Optical disc system and related detecting methods for analysis of microscopic structures

ABSTRACT

An optical disc system includes a photo detector circuit of an optical disc drive and a signal processing system. The photo detector circuit is configured to generate at least one information-carrying signal from an optical disc assembly. The signal processing system is coupled to the photo detector circuit to obtain from the at least one information-carrying signal both operational information used to operate the optical disc system and data indicative of presence and/or characteristics of an investigational feature associated with the optical disc assembly. Methods and discs for imaging a biological or medical investigational feature are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. applicationSer. No. 10/043,688 filed Jan. 10, 2002, which is a continuation-in-partof U.S. application Ser. No.10/008,156 filed Nov. 9, 2001.

[0002] This application also claims the benefit of priority from U.S.Provisional Application Nos. 60/305,043 filed the Jul. 12, 2001,60/307,487 filed Jul. 24, 2001, and 60/322,863 filed Sep. 12, 2001.These applications are herein incorporated by reference in theirentireties.

BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates generally to optical discs andoptical disc readers. In particular, the invention relates to the use ofstandard optical disc drives, and slightly modified drives, to permitdiscriminable acquisition of a variety of different types of signalsfrom an optical disc. The optical discs in such use include opticalbio-discs having encoded information as well as investigationalstructures or features that are deposited on external or internalsurfaces of the disc.

[0005] B 2. Description of Related Art

[0006] Commonly assigned, co-pending U.S. patent application Nos.09/183,842 and 09/311,329 describe methods and apparatus for detectingoperational and investigational structures on one or more surfaces of anoptical disc assembly. Some of the methods and apparatus discussed inthese applications detect investigational structures by physicallymodifying certain processing circuits in the optical disc drives. As analternative to these and similar approaches, the present invention isdirected to utilizing a principal advantage of relying on standardoptical disc readers for laser microscopic detection. This advantageincludes the ubiquitous distribution of such drives in the currentconsumer environment. Therefore, it would be desirable to providemethods and apparatus for detecting operational and investigationalstructures on an optical disc assembly without having to physicallymodify the processing circuitry herein.

[0007] To provide some background for further discussion of the presentinvention, relevant features of a conventional optical disc reader andoptical disc are described briefly in connection with FIGS. 1-7. Forpurposes of preliminary introduction these figures will be brieflydescribed. FIG. 1 is a cross-sectional view of typical single-layer CDor CD-like disc and a schematic representation of a reader associatedtherewith. FIG. 2 is a side cross-sectional view of the disc shown inFIG. 1 at greater magnification. FIG. 3 is a perspective view of thesurface of a CD-R disc with wobble grooves. FIG. 4 is a schematicrepresentation of an optical disc detector and associated electronicsthat use three beams for tracking, focusing, and reading. FIG. 5 is aplan view that illustrates the position of beams from a typicalthree-beam pickup relative to a track on an optical disc. FIG. 6 is ablock diagram of a known optical disc reader. And, FIG. 7 is afunctional block diagram of a conventional digital signal processingcircuit.

[0008] More particularly now, FIG. 1 depicts the reader's optical pickupor objective assembly 10 and a conventional CD-type optical disc 11 witha light path indicated as dashed lines. For clarity, FIG. 1 depicts aminimal complement of the optical pickup components. FIG. 2 provides aside cross-sectional enlarged view of disc 11 in the same orientationrelative to the incident light.

[0009] With reference to FIGS. 1 and 2, the conventional optical pickup10 includes light source 19, lenses 12, 13, and 14, beam splitter 15,quarter wave plate 20, and detector 18. Light source 19 is placed at afocal point of a collimator lens 12 that normally has a long focaldistance. Collimator lens 12 makes the divergent light rays parallel. Amonitor diode (not shown) may be used to stabilize the laser's output.Light source 19 may be a laser, LED, or laser diode, although thepresent invention may be implemented on a non-coherent light system aswell.

[0010] A conventional optical design used for three-beam pickuptypically uses two secondary beams for tracking. To generate thesebeams, light from source 19 passes through diffraction grating 17, whichis a screen with slits spaced only a few laser wavelengths apart. As thebeam passes through the grating, the light diffracts; when the resultingcollection is again focused, it will appear as a single, bright,centered beam with a series of successively less intense beams on eitherside. It is this diffraction pattern that actually strikes the disc.

[0011] A conventional three-beam pickup uses the center beam for readingdata and focusing and two secondary beams for tracking only. In thisdesign, the beams are spatially linked because they are the result of asingle diffracted laser beam. By contrast, a one-beam pickupaccomplishes all of these tasks using a single beam.

[0012] Polarization beam splitter 15 (PBS) directs the light to a discsurface and then directs the reflected light to the photodiode sensor18. PBS 15 normally includes two prisms with a common 45° face acting asa polarizing prism. Collimator lens 12 preferably follows PBS 15. Thelight then passes through the quarter-wavelength plate 20, which is ananisotropic material that rotates the plane of polarization of the lightbeams. Light that has passed through quarter-wavelength plate 20 andthat has been reflected from disc 11 back again throughquarter-wavelength plate 20 will be polarized in a plane at right anglesto that of the incident light. Because PBS 15 passes light in one plane,(e.g., horizontally polarized) but reflects light in the other plane(e.g., vertically polarized), PBS 15 deflects the reflected beam towardsensor 18 to read the digital data.

[0013] The final piece of optics in the optical path to disc 11 isobjective lens 13, which is used to focus the beams onto the disc datasurface, taking into account the refractive index of the light-proximalpolycarbonate substrate 112 of disc 11. Objective lens 13 focuses thelight into a convergent cone of light, or light spot. The convergence isa function of the numerical aperture of the lens.

[0014] The data encoded on disc 11 now determines the fate of the laserlight. In a regular CD, when the light spot strikes a land, the smoothinterval between two pits, light is almost totally reflected. When itstrikes a pit with a depth of about a quarter wavelength of the light,diffraction and cancellation due to interference cause less light to bereflected. All three intensity-modulated light beams return throughobjective lens 13, quarter-wavelength plate 20, collimator 12, and PBS15. Finally, these beams pass through singlet lens 14 and an astigmaticelement 16, which may be a cylindrical lens, to introduce astigmatism inthe reflected light beam en route to photodiode 18.

[0015] As shown in greater detail in FIG. 2, CD-type disc 11 includesthree layers from the light-proximal surface to the light-distalsurface. By convention, disc layers are numbered upwards from thelight-proximal surface to the light-distal surface. These layers includethe transparent substrate 112, a reflective layer 114, and a protectivelayer 116. Transparent substrate 112 makes up most of the thickness of atypical CD-type disc, as measured along the optical axis, and providesboth optical and structural features necessary for disc operation.

[0016] Transparent substrate 112 is typically impressed or embossed witha spiral track that starts at the innermost readable portion of the discand then spirals out to the outermost readable portion of the disc. In anon-recordable disc (e.g., pre-recorded), this track is made up of aseries of embossed pits, each typically having a depth of approximatelyone-quarter the wavelength of the light that is used to read the disc.The pits have varying lengths. The length and spacing of the pits isemployed as the mechanism for encoding the data.

[0017] With reference now to FIG. 3, the spiral groove in a recordabledisc contains a dye rather than pits. A typical recordable disc includesa spiral groove having a characteristic shape along the length thereof.This type of groove is known as a “wobble groove,” and is formed by abottom portion having undulating or wavy sidewalls. A raised or elevatedportion separates adjacent grooves in the spiral. Such a wobble groovemay then include embossed portion 110 and groove portion 118 as shown inFIG. 3. Embossed portion 110 and groove portion 118 are similar to thewobble groove found on a standard recordable CD.

[0018] Referring now to FIG. 4, the exemplary detector 18 and itsassociated electronics are described in more detail. Detector 18typically includes a central detector 25, and can be bordered byadditional side detector elements 26 and 27. Central detector 25 may besplit into multiple detector elements (e.g., four), represented as A, B,C, and D. Detector elements A, B, C, and D (sometimes collectivelyreferred to as a “quad detector”) each provide an electrical signalindicative of the intensity of the reflected light beam striking thatelement.

[0019] The sum of the signals from the quad detector 25, e.g., A+B+C+D,provides a radio frequency (RF) signal 50, also referred to as a highfrequency (HF), quad-sum, or sum signal. As used herein the notation“A+B” indicates the sum of the signals from detector elements A and B.The HF signal 50 (i.e., RF, quad-sum, or sum signal) is typicallydemodulated to recover data recorded on the optical disc.

[0020] Various pairs of the signals from detector elements A to F arealso combined to provide feedback signals for tracking and focuscontrol. For example, a tracking signal 52 (e.g., tracking error or TEsignal) is obtained from the difference between the E and F signals,(i.e., E−F). A focus error (FE) signal 54 may be obtained from thedifference between the A+C and B+D signals.

[0021] Typically, such processing is performed by analog circuitry incombination with one or more integrated circuit chips. Often, thecircuitry takes the form of a special chip set or a single ASIC(application-specific integrated circuit) chip.

[0022] The circuitry of FIG. 4 is just one example of circuitry thatprovides focus and tracking error signals in an optical disc player.Numerous methods are known for providing these signals. For example, afocus error signal may be obtained by the critical angle method,described in U.S. Pat. No. 5,629,514 or the Foucault and astigmatismmethods, described in The Compact Disc Handbook by Pohlmann, A-REditions, Inc. (1992) both of which are incorporated herein by referencein their entireties. Similarly, tracking error signals may be obtainedusing the single beam push-pull or three beam methods described in TheCompact Disc Handbook or the differential phase method described in U.S.Pat. No. 5,130,963, which is incorporated herein by reference in itsentirety, or the single beam high frequency wobble method.

[0023] With reference now to FIG. 5, a CD drive typically uses athree-beam pickup, in which the light beam is split into three beams, amain beam 21 and two tracking beams 23. The main beam 21 is focused ontothe surface of an optical disc so that it is centered on a trackingstructure, whereas the tracking beams 23 fall on opposite sides of thetracking structure. Main beam 21 is shown centered on track 24 (asdefined by pits 22), with tracking beams 23 falling on opposite sides oftrack 24. By design, the three beams are reflected from the optical discand directed to detector 18 (FIG. 4) so that main beam 21 falls on thequad detector, and tracking beams 23 fall on sensor elements E and F.

[0024]FIG. 6 is a generalized block diagram of an illustrative chip set30 for a typical optical drive system. Although the chip sets for CD,CD-R, and DVD drives can be somewhat different from one another, it willbe understood that the system shown in FIG. 6 is meant to genericallyrepresent all types of optical drives, and that a detailed understandingof the differences between the chip sets is not necessary to practicethe present invention.

[0025] The HF signal 50, obtained from summing the signals from detectorelements A, B, C, and D, is normally processed to extract whatever datais recorded on the optical disc. First, analog HF signal 50 isconditioned, with normalization and equalization performed. Next, analogsignal 50 is converted to a digitized signal including a serial streamof digital data referred to as channel bits. The channel bit stream isthen demodulated according to the modulation standard used for the typeof optical disc being read. For example, it is common for CD-type discsto use eight-to-fourteen (also denominated “eight-of-fourteen”)modulation (EFM) wherein a data byte, or eight data bits, is encodedinto fourteen channel bits. There are three merging bits between eachgroup of fourteen channel bits. Thus, when reading a CD-type opticaldisc, seventeen channel bits are read from the optical disc, the mergingbits are discarded, and the remaining fourteen bits are decoded, ordemodulated, to obtain the original data byte. The data bytes themselvesare grouped into blocks, which are further processed to reduce theeffects of disc defects, such as scratches on the disc surface.

[0026] HF signal 50 from detector 18 (FIG. 4) may be converted to asquare wave signal 51 by comparator 31, which provides a high outputwhen HF signal 50 is above a threshold level, and a low output when HFsignal 50 is below the threshold. Digital signal processing circuit(DSP) 32 then samples the resulting square wave signal 51 to determinethe value of each channel bit. DSP 32 further demodulates the channelbits to extract the data bytes that are then grouped into blocks andprocessed to correct errors that may have occurred. Memory 33 a providestemporary storage for the data, as it is being processed by DSP 32 andassembled into blocks.

[0027] Servo block 34 analyzes the tracking error (TE) signal 52 (or awobble tracking error (WTE) in a DVD or CD-R system) and provides atracking control signal to the tracking mechanisms to ensure that thepickup assembly maintains proper tracking. Similarly, a focus controlsignal 53 is provided based on focus error (FE) signal 54. DSP 32provides an indication of the data rate of HF signal 50, which is usedby servo block 34 to provide a speed control signal 55 to the spindlemotor (not shown) of the optical disc drive.

[0028] In an audio CD player, after processing by DSP 32, each datablock is sent to audio reproduction circuitry not shown in FIG. 6.However, in some data storage applications, each data block may containadditional error detection codes (EDC) and error correction codes (ECC).EDC/ECC circuitry 35 typically uses the EDC and ECC codes to increasethe integrity of the data block by detecting and correcting errors notalready corrected by DSP 32. Memory 33 b, which may be combined withmemory 33 a, provides temporary storage for data blocks being processedby EDC/ECC circuitry 35. Finally, the data blocks are transferred fromthe optical disc player to host 37 by means of interface circuitry 36.Although an ATAPI interface is shown, it will be understood that otherinterfaces, such as SCSI, Firewire, or Universal Serial Bus (USB) andthe like could also be used.

[0029] A controller 38 coordinates the operation of the variouscomponents of chip set 30, for example, by coordinating the transfer ofdata blocks between DSP 32 and EDC/ECC circuitry 35. Controller 38 alsokeeps track of which data block is being read and may keep track ofvarious parameters indicative of the operational status of the opticaldisc reader.

[0030] Program memory 39 contains program code for the operation ofcontroller 38. In many optical disc reader chip sets, program memory 39may also contain program instructions for DSP 32 or EDC/ECC circuitry35. This is advantageous for manufacturers in that the operation of thedisc drive may be changed by altering the program code in program memory39. For example, a newly developed method of modulating or encoding dataon an optical disc may be accommodated by changing program memory 39.

[0031]FIG. 7 is a functional block diagram illustrating the signalprocessing that occurs within DSP chip 32 when configured in aconventional manner. As shown, DSP 32 performs several functions. Forexample, DSP 32 typically normalizes and/or equalizes the HF signal(block 40); converts the normalized HF signal from the analog-to-digital(block 42); demodulates and decodes the resulting EFM signal (block 44);performs some type of error checking procedure (e.g., usingCross-Interleaved Reed-Solomon Code “CIRC” block 46); and provides theresulting signal to an output interface (block 48) for communicationwith the host data bus 37 (FIG. 6). Examples of commonly used DSP chipsthat perform some or all of these functions include the SAA 7210, SAA7220, and the SAA 7735, available from Philips Electronics Corporation,Eindhoven, Netherlands.

[0032] While the foregoing description is sufficient for a basicunderstanding of the present invention, there are numerous alternativedesigns and configurations of an optical pickup and associatedelectronics, which may be used in the context of the present invention.Further details and alternative designs are described in Compact DiscTechnology, by Nakajima and Ogawa, IOS Press, Inc. (1992); The CompactDisc Handbook, Digital Audio and Compact Disc Technology, by Baert etal. (eds.), Books Britain (1995); CD-Rom Professional's CD-RecordableHandbook: The Complete Guide to Practical Desktop CD, Starrett et al.(eds.), ISBN:0910965188 (1996); all of which are incorporated herein intheir entirety by this reference.

SUMMARY OF THE INVENTION

[0033] It is an object of the present invention to overcome limitationsin the known art. It is a further object of the present invention toadapt a known optical disc system to read an optical disc assembly andextract both operational information used to operate the optical discsystem and indicia data indicative of a presence of an investigationalfeature associated with the optical disc assembly.

[0034] These and other objects and advantages of the present inventionare achieved in an optical disc system that includes a photo detectorcircuit of an optical disc drive and a signal processing system. Thephoto detector circuit of the optical disc drive is configured togenerate at least one information-carrying signal from an optical discassembly. The signal processing system is coupled to the photo detectorcircuit to obtain from the at least one information-carrying signal bothoperational information used to operate the optical disc system, andindicia or characteristic data indicative of a presence of aninvestigational feature associated with the optical disc assembly.

[0035] The present invention is also directed to a method that includesdepositing a test sample, spinning the optical disc assembly, directingan incident beam, detecting a return beam, and processing the detectedreturn beam to acquire information about an investigational featureassociated with the test sample. The step of depositing a test samplepositions the sample at a predetermined location on an optical discassembly. The step of spinning the optical disc assembly is directed tospinning the disc assembly in an optical disc drive. The step ofdirecting an incident beam directs the beam onto the optical discassembly. The step of detecting a return beam detects the returned beamformed as a result of the incident beam interacting with the testsample.

[0036] Other advantages of the present invention are achieved in analternative method that includes acquiring a plurality of analogsignals, summing a first subset of the plurality of analog signals,combining a second subset of the plurality of analog signals, obtaininginformation used to operate an optical disc drive, and converting thesum signal to a digitized signal. The step of acquiring a plurality ofanalog signals includes receiving return light from the optical discassembly using a plurality of photo detectors. The step of summing afirst subset of the plurality of analog signals produces a sum signal.The step of combining a second subset of the plurality of analog signalsproduces a tracking error signal. The step of obtaining information usedto operate the optical disc drive includes processing the tracking errorsignal.

[0037] An alternative method of the present invention includes adaptinga portion of a signal processing system, acquiring a plurality on analogsignals, converting the analog signals into a digitized signal, andcharacterizing investigational features on an optical disc assemblybased on the digitized signal. The step of adapting a portion of asignal processing system adapts the system to operate as ananalog-to-digital converter. The step of acquiring a plurality on analogsignals acquires the signals from a photo detector circuit of an opticaldisc drive. The plurality of analog signals include information that isindicative of the investigational features. The step of converting theanalog signals into a digitized signal converts the signals using thesignal processing system.

[0038] A specific implementation of this method includes steps ofreceiving and converting. The step of receiving includes receiving atleast one analog signal at a corresponding input of signal processingcircuitry. The at least one analog signal is provided by at least onecorresponding photo detector element that detects light returned from asurface of the optical disc assembly. The step of converting includesconverting each of the at least one analog signal into a correspondingdigitized signal. Each digitized signal is substantially proportional toan intensity of the returned light detected by a corresponding one ofthe at least one photo detector elements.

[0039] More specifically, the present invention is directed to anoptical disc system including a photo detector circuit of an opticaldisc drive configured to generate at least one information-carryingsignal from an optical disc assembly. The optical disc system is furtherprovided with a signal processing system coupled to the photo detectorcircuit to obtain from the at least one information-carrying signal bothoperational information used to operate the optical disc system andindicia data indicative of a presence of an investigational featureassociated with the optical disc assembly.

[0040] In one embodiment, the signal processing system includes a PC andanalog-to-digital converter coupled between the at least one informationcarrying signal and the PC. The analog-to-digital converter mayadvantageously provide a digitized signal and the PC may include a firstprogram module to detect and characterize peaks in the digitized signal.In this embodiment, the PC may further include a second program moduleto detect and count double peaks in the digitized signal. In addition,the signal processing system may also further include an analyzercoupled between the analog-to-digital converter and the PC. In thisembodiment, the analog-to-digital converter provides a digitized signal,and the analyzer includes logic to detect and characterize peaks in thedigitized signal. According to one aspect of this embodiment, theanalyzer further includes logic to detect and count double peaks in thedigitized signal.

[0041] Alternatively, the optical disc system may include a signalprocessing system that has an audio processing module coupled betweenthe at least one information-carrying signal and the analog-to-digitalconverter. In this alternate implementation, the optical disc systemfurther includes a predetermined sound recorded on the optical discassembly, and a program module in the PC for detecting the indicia datain a deviation of the at least one information carrying signal from thepredetermined sound when the investigational feature is present. Thepredetermined sound may be encoded silence.

[0042] In another embodiment, the signal processing system furtherincludes a buffer coupled between the at least one information-carryingsignal and the analog-to-digital converter. The signal processing systemmay further advantageously include a trigger detection circuit coupledto the analog-to-digital converter, the trigger detection circuit beingoperative to detect a particular time in relation to a time when theindicia data is present in the at least one information-carrying signal.

[0043] In yet another implementation of the present invention, thesignal processing system includes a programmable digital signalprocessor selectively configurable to extract the operationalinformation from the at least one information-carrying signal while in afirst configuration and operate as an analog-to-digital converter toprovide the indicia data while in a second configuration. According toan aspect of this implementation of the invention, the signal processingsystem may include a PC, a programmable digital signal processor coupledto the at least one information-carrying signal, and an analyzer coupledbetween the programmable digital signal processor and the PC so that theanalyzer provides the indicia data.

[0044] In many of the specific implementations and embodiments of thepresent invention, the signal processing system may advantageously beprovided with a trigger detection circuit that detects a time periodduring which the investigational feature associated with the opticaldisc assembly is scanned by the photo detector circuit, or alternativelya trigger detection circuit that detects a particular trigger time inrelation to a respective time duration during which the indicia data ispresent in the at least one information-carrying signal, and eachrespective time duration occurs periodically with a respectiveinvestigational feature and a corresponding set of indicia data.

[0045] According to one aspect of the audio implementation of thisinvention, the signal processing system includes a PC and an audioprocessing module coupled between the PC and the at least oneinformation-carrying signal. The audio processing module may be selectedone of either an external module independent of the optical disc drive,a drive module that is a part of the optical disc drive, or a modifieddrive module that is a part of the optical disc drive. The PC mayadvantageously include a processor coupled to the audio module, and asoftware module stored in a memory to control the processor to extractthe indicia data from audio data.

[0046] In one principal embodiment of the present invention, the photodetector circuit includes circuitry to generate an analog signal as theat least one information-carrying signal. The analog signal includingone of a high frequency signal from a photo detector, a tracking errorsignal, a focus error signal, an automatic gain control setting, apush-pull tracking signal, a CD tracking signal, a CDR tracking signal,a focus signal, a differential phase detector signal, a laser powermonitor signal, and a sound signal.

[0047] According to other aspects of this invention, the optical discsystem may include an optical disc assembly having disposed thereon theassociated investigational feature in a first disc sector and encodedthereon the operational information used to operate the optical discdrive in a remaining disc sector. The optical disc assembly may includea reflective-type or transmissive-type optical disc. The optical discassembly may include a trigger mark disposed thereon in a predeterminedposition relative to the first disc sector. In this embodiment, thesignal processing system includes a trigger detection circuit thatdetects the trigger mark.

[0048] In accordance with certain aspects hereof, the trigger detectioncircuit detects the trigger mark periodically. The trigger detectioncircuit may detects the trigger mark either at (i) a predetermined timein advance of, (ii) a time at, or (iii) a predetermined time after atime when a respective investigational feature is read by the photodetector circuit based on the predetermined position of the trigger markrelative to the first disc sector.

[0049] In alternative designs of one principal embodiment of the opticaldisc system, one or more additional photo detector circuits areconfigured to generate at least one information-carrying signal from arespective optical disc assembly. The optical disc assembly may includeone or more reporters having an affinity for a respectiveinvestigational feature. One or more of the reporters may beindividually selected from the group consisting of plasticmicro-spheres, colloidal gold beads, silica beads, glass beads, latexbeads, polystyrene beads, magnetic beads, and fluorescent beads.

[0050] According to another aspect of the present invention, there isprovided an assay method which includes the steps of (1) depositing atest sample at a predetermined location on an optical disc assembly, (2)spinning the optical disc assembly in an optical disc drive, (3)directing an incident beam onto the optical disc assembly, (4) detectinga return beam formed as a result of the incident beam interacting withthe test sample, and (5) processing the detected return beam to acquireinformation about an investigational feature associated with the testsample. In this method the optical disc assembly may include one or morereporters having an affinity for investigational features in the testsample. These reporters may be individually selected from the groupconsisting of plastic micro-spheres, colloidal gold beads, silica beads,glass beads, latex beads, polystyrene beads, magnetic beads, andfluorescent beads.

[0051] In this embodiment of the present method, the step of detecting areturn beam may form a plurality of analog signals. The step ofprocessing the detected return beam may advantageously include (1)summing a first subset of the plurality of analog signals to produce asum signal (2) combining one of the first subset and a second subset ofthe plurality of analog signals to produce a tracking error signal, (3)obtaining information used to operate an optical disc drive from thetracking error signal, and (4) converting the sum signal to a digitizedsignal. This method may optionally include the additional step ofdetecting a trigger mark associated with the optical disc assembly.

[0052] Another assay method according to certain aspects of thisinvention includes the steps of (1) depositing a test sample at apredetermined location on an optical disc assembly (2) spinning theoptical disc assembly in an optical disc drive, (3) directing anincident beam onto the optical disc assembly, (4) detecting atransmitted beam formed as a result of the incident beam interactingwith the test sample and continuing through the disc assembly, and (5)processing the detected transmitted beam to acquire information about aninvestigational feature associated with the test sample. This method mayinclude the further steps of detecting a reflected beam formed as aresult of the incident beam interacting with the test sample, andprocessing the detected reflected beam to acquire information about aninvestigational feature associated with the test sample. This method mayalso include the optical disc assembly having one or more reporters withan affinity for investigational features in the test sample. As with theprior method discussed above, in this method the one or more reportersmay be individually selected from the group consisting of plasticmicro-spheres, colloidal gold beads, silica beads, glass beads, latexbeads, polystyrene beads, magnetic beads, and fluorescent beads.

[0053] Also in this method, the step of detecting a transmitted beamforms a plurality of analog signals. Similarly, the step of processingthe transmitted beam may include the additional steps of (1) summing afirst subset of the plurality of analog signals to produce a sum signal,(2) combining one of the first subset and a second subset of theplurality of analog signals to produce a tracking error signal, (3)obtaining information used to operate an optical disc drive from thetracking error signal, and (4) converting the sum signal to a digitizedsignal. This method may optionally include the additional step ofdetecting a trigger mark associated with the optical disc assembly.

[0054] Yet another method of this invention includes the steps of (1)acquiring a plurality of analog signals from an optical disc assemblyusing one or more photo detectors, (2) summing a first subset of theplurality of analog signals to produce a sum signal, (3) combining asecond subset of the plurality of analog signals to produce a trackingerror signal, (4) obtaining information used to operate an optical discdrive from the tracking error signal, and (5) converting the sum signalto a digitized signal. In this alternative method, the steps ofacquiring and summing produce the sum signal, and the sum signalincludes perturbations indicative of an investigational featurepositioned at a location on the optical disc assembly. This method mayinclude the further step of characterizing the investigational featurebased on the digitized signal.

[0055] In this method, the step of converting may include configuring aportion of an optical disc drive chip set to operate as ananalog-to-digital converter. In one embodiment, this configuring stepincludes programming a digital signal processing chip within the opticaldisc drive chip set to operate as an analog-to-digital converter. Thedigital signal processing chip may advantageously be provided with anormalization function, an analog-to-digital converter function, ademodulation/decode function, and an output interface function. In thisspecific embodiment, the step of configuring may further includeby-passing the sum signal around the demodulation/decode function bycreating a path from the analog-to-digital converter function to theoutput interface function. And, the step of configuring may also includedeactivating the demodulation/decode function.

[0056] According to one principal aspect of this method, the step ofconverting includes configuring a digital signal processing chip thatincludes a normalization function, an analog-to-digital converterfunction, a demodulation/decode function, and an output interfacefunction. And, the step of configuring includes creating a path from theanalog-to-digital converter function to the output interface function sothat the sum signal is unprocessed by the demodulation/decode function.Herein, the step of configuring may similarly include deactivating thedemodulation/decode function.

[0057] In accordance with one aspect of this method, the step ofacquiring may include tapping one or more of the plurality of analogsignals directly at the one or more photo detectors. And, the step ofconverting may include directing the signals into an analog-to-digitalconverter. In a particular embodiment, the step of converting furtherincludes directing the analog signals from the one or more photodetectors into a buffer amplifier before processing by theanalog-to-digital converter.

[0058] Alternatively, the step of acquiring may include tapping one ormore of the plurality of analog signals after processing by an opticaldisc drive chip set, while the step of converting may then includedirecting the signals into an analog-to-digital converter. In thisalternative embodiment, the step of converting may similarly includedirecting the analog signals from the optical disc drive chip set into abuffer amplifier before directing the analog signals into theanalog-to-digital converter.

[0059] According to still another aspect of this invention, there isprovided an alternative method including the steps of (1) adapting aportion of a signal processing system to operate as an analog-to-digitalconverter (2) acquiring a plurality of analog signals from a photodetector circuit of an optical disc drive, the plurality of analogsignals including information therein that is indicative ofinvestigational features on an optical disc assembly (3) converting theanalog signals into a digitized signal with the signal processingsystem, and (4) characterizing the investigational features based on thedigitized signal. In this embodiment, the step of adapting may includeprogramming a digital signal processing chip within the signalprocessing system to operate as the analog-to-digital converter.

[0060] Still yet a further method according to this invention includesthe steps of (1) receiving each of at least one analog signal at acorresponding input of signal processing circuitry, the at least oneanalog signal having been provided by at least one corresponding photodetector element that detects light returned from a surface of anoptical disc assembly, and (2) converting each of the at least oneanalog signal into a corresponding digitized signal, each digitizedsignal being substantially proportional to an intensity of the returnedlight detected by a corresponding one of the at least one photo detectorelement. In this method, the step of converting may advantageouslyinclude operating the signal processing circuitry to bypass anydemodulation of a first digitized signal. In this embodiment, the stepof converting may further include the steps of (1) operating the signalprocessing circuitry to bypass any decoding of the first digitizedsignal, and (2) operating the signal processing circuitry to bypass anychecking for errors in the first digitized signal.

[0061] Alternatively, the step of converting may include operating thesignal processing circuitry to bypass any decoding of a first digitizedsignal. As an alternative thereto, the converting step may includeoperating the signal processing circuitry to bypass any checking forerrors in a first digitized signal.

[0062] The different embodiments of this method may each include thefurther step of combining at least two of the at least one analog signalwhen there are two or more such signals. In this embodiment, the step ofcombining is a step selected from a group consisting of adding,subtracting, dividing, and multiplying, and any combination thereof. Thestep of combining may be performed before, or alternatively after, thestep of converting.

[0063] The method of claim 55 wherein the step of receiving includes atleast one analog signal provided by at least one corresponding photodetector element that detects light transmitted through an optical discassembly.

[0064] Generally for this method, the step of receiving may includedetection of a trigger mark indicative of a time period during which theinvestigational feature associated with the optical disc assembly isscanned by the at least one photo detector. Also any of theseembodiments may further include a step of supplying a first digitizedsignal of the at least one digitized signal at an output interface ofthe signal processing circuitry after the step of converting withoutsubstantially modifying the first digitized signal between the steps ofconverting and supplying. In these embodiments, the signal processingcircuitry includes a digital signal processor or, alternatively, anexternal analog-to-digital converter. In the A/D converterimplementation, the signal processing circuitry may further include abuffer amplifier before the external analog-to-digital converter.

[0065] According to other aspects of this invention, the characteristicsignals generated hereby are considered inventive in their own right.Thus the present invention is further directed to a signalcharacteristic of information about an investigational feature locatedin an optical disc assembly, the signal being generated by a processincluding the steps of (1) depositing a test sample at a predeterminedlocation on an optical disc assembly, (2) spinning the optical discassembly in an optical disc drive, (3) directing an incident beam ontothe optical disc assembly, (4) detecting a return beam formed as aresult of the incident beam interacting with the test sample, and (5)processing the detected return beam to acquire information about aninvestigational feature associated with the test sample. The return beammay be formed as a result of the incident beam interacting with one ormore reporters having an affinity for investigational features in thetest sample. The step of detecting the return beam may form a pluralityof analog signals. In this embodiment, the step of processing thedetected return beam may include (1) summing a first subset of theplurality of analog signals to produce a sum signal, (2) combining oneof the first subset and a second subset of the plurality of analogsignals to produce a tracking error signal, (3) obtaining informationused to operate an optical disc drive from the tracking error signal,and (4) converting the sum signal to a digitized signal. The signal maythen include distinctive perturbations indicative of an investigationalfeature located at a location of the optical disc assembly. As above,the step of converting may include configuring a portion of an opticaldisc drive chip set to operate as an analog-to-digital converter. And,the step of configuring may include programming a digital signalprocessing chip within the optical disc drive chip set to operate as ananalog-to-digital converter.

[0066] In one specific embodiment of the process employed to generatethe desired signal, the digital signal processing chip includes anormalization function, an analog-to-digital converter function, ademodulation/decode function, and an output interface function. In thisembodiment, the step of configuring may further comprises passing thesum signal around the demodulation/decode function by creating a pathfrom the analog-to-digital converter function to the output interfacefunction. Also, the step of configuring may further include deactivatingthe demodulation/decode function.

[0067] In another specific embodiment of the process employed togenerate the desired signature signals, the step of converting mayinclude directing the sum signal into an external analog-to-digitalconverter. In this embodiment, the step of converting may furtherinclude directing the sum signal into a buffer amplifier prior to theexternal analog-to-digital converter.

[0068] In yet a further specific embodiment of the process employed togenerate the desired signal signatures, the step of converting mayinclude configuring a digital signal processing chip that includes anormalization function, an analog-to-digital converter function, ademodulation/decode function, and an output interface function, whilethe step of configuring includes creating a path from theanalog-to-digital converter function to the output interface function sothat the sum signal is unprocessed by the demodulation/decode function.

[0069] In many of these signal generating processes, the step ofdetecting may further include detecting a transmitted beam formed as aresult of the incident beam interacting with the test sample and passingthrough the optical disc assembly.

[0070] Additionally, the step of detecting the return beam may form aplurality of analog signals and the step of processing the detectedreturn beam may include (1) summing a first subset of the plurality ofanalog signals to produce a sum signal, (2) combining a second subset ofthe plurality of analog signals to produce a tracking error signal, (3)obtaining information used to operate an optical disc drive from thetracking error signal, and (4) converting the sum signal to a digitizedsignal. In these embodiments, the sum signal advantageously includesperturbations indicative of an investigational feature located at alocation of the optical disc assembly.

[0071] The step of converting may include configuring a portion of anoptical disc drive chip set to operate as an analog-to-digitalconverter. In these embodiments, the step of configuring may includeprogramming a digital signal processing chip within the optical discdrive chip set to operate as an analog-to-digital converter. In a morespecific implementation thereof, the digital signal processing chipincludes a normalization function, an analog-to-digital converterfunction, a demodulation/decode function, and an output interfacefunction. In these specific embodiments, the step of configuring mayfurther include passing the sum signal around the demodulation/decodefunction by creating a path from the analog-to-digital converterfunction to the output interface function. Also, the step of configuringmay further include deactivating the demodulation/decode function.

[0072] In certain embodiments of the process for generation the desiredsignal signatures, the step of converting includes configuring a digitalsignal processing chip that includes a normalization function, ananalog-to-digital converter function, a demodulation/decode function,and an output interface function, while the step of configuringcomprises creating a path from the analog-to-digital converter functionto the output interface function so that the sum signal is unprocessedby the demodulation/decode function.

[0073] The unique signal signatures of the present invention may also begenerated by a process including the steps of (1) adapting a portion ofa signal processing system to operate as an analog-to-digital converter,(2) acquiring a plurality of analog signals from a photo detectorcircuit of an optical disc drive, wherein the plurality of analogsignals includes information therein that is indicative ofinvestigational features on an optical disc assembly, (3) converting theanalog signals into a digitized signal with the signal processingsystem, and (4) characterizing the investigational features based on thedigitized signal. In this process, the step of adapting may includeprogramming a digital signal processing chip within the signalprocessing system to operate as the analog-to-digital converter. Also,the step of acquiring may include tapping the analog signals prior to anoptical drive buffer. And, the step of acquiring may include triggermark signals indicative of a time period during which theinvestigational feature associated with the optical disc assembly isscanned by the photo detector circuit.

[0074] According to still other aspects of this invention, there isprovided a method of detecting a signal within an optical disc system,which method includes the steps of (1) generating an incident beam ofknown wavelength, (2) directing the beam onto an optical disc containingan investigational feature, and (3) receiving a return beam formed as aresult of the incident beam interacting with the investigationalfeature. In this method the optical disc may comprise one or morereporters having an affinity for the investigational feature, thereporters being capable of interacting with the incident beam. One ormore of the reporters may be individually selected from the groupconsisting of plastic micro-spheres, colloidal gold beads, silica beads,glass beads, latex beads, polystyrene beads, magnetic beads, andfluorescent beads. Also in this method, the step of receiving mayfurther include receiving a transmitted beam formed as a result of theincident beam interacting with the investigational feature, and passingthrough the optical disc. Generally, the step of receiving mayadvantageously involve use of one or more photo detectors. The step ofreceiving may form a plurality of analog signals for processing by asignal processing system. In addition, the signal processing system mayinclude an external analog-to-digital converter and with or without abuffer amplifier associated therewith. In the embodiment utilizing thebuffer amplifies, the analog signals may be tapped prior to processingby an internal optical disc drive buffer circuit. In certainimplementations of these aspects of the present invention, the signalprocessing system may include programmable digital signal processingcircuitry or audio processing circuitry.

[0075] According to yet still additional aspects of the presentinvention, there is provided a method of imaging an investigationalfeature including the steps of (1) depositing an investigational featureat a predetermined location on an optical disc assembly, (2) spinningthe optical disc assembly in an optical disc drive, (3) directing anincident beam onto the optical disc assembly, (4) detecting a returnbeam formed as a result of the incident beam interacting with theinvestigational feature, (5) processing the detected return beam toacquire information about an investigational feature, and (6) imagingthe investigational feature based on the information. In this method,the optical disc assembly may be provided with one or more reportershaving an affinity for investigational features in the test sample. Theone or more reporters may be individually selected from the groupconsisting of plastic micro-spheres, colloidal gold beads, silica beads,glass beads, latex beads, polystyrene beads, magnetic beads, andfluorescent beads. Also in this method, the step of detecting the returnbeam may form a plurality of analog signals, and the step of processingcomprises converting the analog signals into a digitized signal. In thisparticular embodiment, the step of processing involves a signalprocessing system that may include an external analog-to-digitalconverter with or without a buffer amplifier. Alternatively, the signalprocessing system may be provided with programmable digital signalprocessing circuitry and/or related audio processing circuitry.

[0076] In many implementations of this particular method, the step ofprocessing the detected return beam may include the further steps of (1)summing a first subset of the plurality of analog signals to produce asum signal, (2) combining one of the first subset and a second subset ofthe plurality of analog signals to produce a tracking error signal, (3)obtaining information used to operate an optical disc drive from thetracking error signal, (4) converting the sum signal to a digitizedsignal, and (4) outputting the digitized signal. In theseimplementations, the step of outputting may involve displaying thedigitized signal on a monitor or playing the digitized signal as soundusing speakers.

[0077] In accordance with yet still additional aspects of thisinvention, there is provided a kit for the detection of aninvestigational feature in a test sample. The kit includes a carriercompartmentalized to receive one or more optical discs. The kit mayfurther include one or more containers, the containers having one ormore agents selected from the group consisting of isolated nucleicacids, antibodies, proteins, reagents, and reporters. The kit of mayfurther be provided with at least one optical bio-disc according to thepresent invention, and/or a setup optical disc.

[0078] The kit may further include a buffer amplifier card, the cardbeing adapted to retrofit into an optical disc drive. The kit mayalternatively include a modified optical disc drive.

[0079] According to still further aspects of this invention, an opticalanalysis disc for detection of a signal element is provided. This discincludes a substrate layer, an operational layer associated with thesubstrate layer, the operational layer having operational informationencoded therein, and a signal element positioned relative to theoperational layer, the signal element and the operational layer havingoptical or magnetic characteristics selected to provide a predeterminedcontrast therebetween to thereby provide a return signal indicative ofdistinctions between information associated with the operation layer andcharacteristics of the signal element. The optical or magneticcharacteristics include but are not limited to, electrical or magneticpolarization state or irradiance of the signal element and/or theoperational layer.

[0080] In accordance with yet still additional aspects of the presentinvention, there is provided an optical analysis disc for use in imaginga biological or medical investigational feature. This disc includes asubstrate, an operational layer associated with the substrate, theoperational layer having encoded operational features positionedrelative to each other at a specified track pitch, and aninvestigational feature positioned relative to the operational layer,the investigational feature selected to be larger in size than acorresponding operational feature and at least as large in size asone-half of the track pitch to thereby provide at least one scan of theinvestigational feature as an incident beam tracks along the operationalfeatures. In this embodiment, rotational speed of the disc may becontrolled to produce a higher quantized resolution in the digitizationof a return signal generated by the disc. This disc may alsoadvantageously include logic to provide random access to preaddressedlocations on the disc.

BRIEF DESCRIPTION OF DRAWING FIGURES

[0081] Further objects of the present invention together with additionalfeatures contributing thereto and advantages accruing therefrom will beapparent from the following description of the preferred embodiments ofthe invention which are shown in the accompanying drawing with likereference numerals indicating like components throughout, wherein:

[0082]FIG. 1 is a cross-sectional view of typical single-layer CD orCD-like disc and a schematic representation of a reader associatedtherewith;

[0083]FIG. 2 is a side cross-sectional view of the disc shown in FIG. 1at greater magnification;

[0084]FIG. 3 is a perspective view of the surface of a CD-R disc withwobble grooves;

[0085]FIG. 4 is a schematic representation of an optical disc detectorand associated electronics that use three beams for tracking, focusing,and reading;

[0086]FIG. 5 is a plan view that illustrates the position of beams froma typical three-beam pickup relative to a track on an optical disc;

[0087]FIG. 6 is a block diagram of a known optical disc reader;

[0088]FIG. 7 is a functional block diagram of a conventional digitalsignal processing circuit;

[0089]FIG. 8 is a block diagram of a chip set of a generic optical discreader, modified according to one aspect of the present invention tomonitor signals for determining the presence of investigational featuresor structures on an optical analysis disc;

[0090]FIG. 9A is a pictorial representation and block diagramillustrating alternative embodiments of the present invention directedto processing the high frequency, tracking, focusing, audio, or othersignals of a disc drive and displaying or outputting results relatingthereto;

[0091]FIG. 9B is an enlarged detailed perspective view of the sectionindicated in FIG. 9A showing a coordinate reference system used forpurposes of 3 dimensional orientation;

[0092]FIG. 10 is a flow chart depicting a known process for fabricatingoptical discs and then later reading the optical discs;

[0093]FIG. 11 is a modified path for decoding optical discs according tothe present invention;

[0094]FIG. 12 is a view similar to FIG. 9A showing the optical discassembly and investigational features in conjunction with the opticalcomponents and return beam of an optical disc reader and driveimplemented according to a first embodiment of the present invention;

[0095]FIG. 13 is a plan view of a disc showing target zones and ahardware trigger;

[0096]FIG. 14 is a block diagram of an overall drive system according toan embodiment of the present invention;

[0097]FIG. 15 is a top view of a circuit board including a triggeringdetection assembly according to another aspect of the present invention;

[0098]FIG. 16 is an electrical schematic of the triggering circuit shownin FIG. 15;

[0099]FIG. 17 is a part pictorial, part block diagram showing a disc anda reading system as implemented according to certain aspects of thepresent invention;

[0100]FIG. 18 is a block diagram of a board with functionality includinga trigger, an amplifier, and detection circuitry for use in variousembodiments of the present invention;

[0101]FIG. 19 is a top plan view of an optical disc drive assembly withthe housing removed to show the spindle, the carriage assembly, theoptical head assembly, and the ribbon cable or connector which transmitssignals to and from the optical head assembly;

[0102]FIG. 20 is a bottom perspective view of the optical disc driveassembly of FIG. 19, illustrating the physical layout of the chip set,related electronic circuitry, and the ribbon connector from the headassembly as unplugged from the circuitry;

[0103]FIG. 21 is a block diagram illustrating the known optical discreader of FIG. 6 as connected to a buffer card according to differentembodiments of this invention;

[0104]FIG. 22 is a top perspective view of an external buffer amplifiercard adapted to receive signals from the head assembly of the drivebuffer according to a first embodiment of the present invention;

[0105]FIG. 23 is a perspective view of an alternative embodiment of theexternal buffer amplifier card illustrated in FIG. 22;

[0106]FIG. 24 is a graphical representation illustrating therelationship between FIGS. 24A, 24B, and 24C;

[0107]FIGS. 24A, 24B, and 24C are electrical schematics of the amplifierstages according to a first embodiment of the buffer cards shown inFIGS. 22 and 23;

[0108]FIG. 25 is a functional block diagram of a digital signalprocessing circuit programmably configured as an analog-to-digitalconverter in accordance with the principles of an alternate embodimentof the present invention as represented in FIG. 9;

[0109]FIG. 26 is a flow chart illustrating some of the steps involved indetecting investigational elements in accordance with the secondembodiment of the present invention illustrated in FIG. 25;

[0110]FIG. 27 is an exploded perspective view of a reflective bio-discas utilized in conjunction with the present invention;

[0111]FIG. 28 is a top plan view of the disc shown in FIG. 27;

[0112]FIG. 29 is a perspective view of the disc illustrated in FIG. 27with cut-away sections showing the different layers of the disc;

[0113]FIG. 30 is an exploded perspective view of a transmissive bio-discas employed in conjunction with the present invention;

[0114]FIG. 31 is a perspective view representing the disc shown in FIG.30 with a cut-away section illustrating the functional aspects of asemi-reflective layer of the disc;

[0115]FIG. 32 is a graphical representation showing the relationshipbetween thickness and transmission of a thin gold film;

[0116]FIG. 33 is a top plan view of the disc shown in FIG. 30;

[0117]FIG. 34 is a perspective view of the disc illustrated in FIG. 30with cut-away sections showing the different layers of the discincluding the type of semi-reflective layer shown in FIG. 31;

[0118]FIG. 35 is a partial cross sectional view taken perpendicular to aradius of the reflective optical bio-disc illustrated in FIGS. 27, 28,and 29 showing a flow channel formed therein;

[0119]FIG. 36 is a partial cross sectional view taken perpendicular to aradius of the transmissive optical bio-disc illustrated in FIGS. 30, 33,and 34 showing a flow channel formed therein and a top detector;

[0120]FIG. 37 is a partial longitudinal cross sectional view of thereflective optical bio-disc shown in FIGS. 27, 28, and 29 illustrating awobble groove formed therein;

[0121]FIG. 38 is a partial longitudinal cross sectional view of thetransmissive optical bio-disc illustrated in FIGS. 30, 33, and 34showing a wobble groove formed therein and a top detector;

[0122]FIG. 39 is a view similar to FIG. 35 showing the entire thicknessof the reflective disc and the initial refractive property thereof;

[0123]FIG. 40 is a view similar to FIG. 36 showing the entire thicknessof the transmissive disc and the initial refractive property thereof;

[0124]FIG. 41 is a cross sectional side view of an optical disc assemblyincluding a light refractive cover and investigational featuresaccording to the present invention;

[0125]FIG. 42 is a plan view showing a typical three-beam systemprojecting onto three tracks of the disc;

[0126]FIG. 43 is a plan view of three beams relative to three tracks,one of which has an investigational feature positioned thereon accordingto the present invention;

[0127]FIG. 44 is a graph depicting a signal that corresponds to anoperation feature such as a pit or land including discernable changes asexploited by the present invention;

[0128]FIGS. 45 and 46 are graphs depicting changes in signals producedby operational features encountered on the disc;

[0129]FIG. 47 is a section view of a bio-disc according to the presentinvention that shows a micro-fluidic channel;

[0130]FIG. 48 is a representative graph of the change in reflectivity ofmaterials with thickness that is exploited according to the presentinvention;

[0131]FIG. 49 is pair of graphs depicting an envelope of fluctuations ofan analog readout signal that has been enlarged by reaction in amicro-fluidic channel according to the present invention;

[0132]FIG. 50 is a plan view of a bio-disc and corresponding readout oftest sample signals according to the present invention;

[0133]FIG. 51 is a cross-sectional side view of an optical bio-discincluding bead reporters as utilized in conjunction with the presentinvention;

[0134]FIG. 52A is a graphical representation of two 6.8 μm blue beadspositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0135]FIG. 52B is a series of signature traces derived from the beads ofFIG. 52A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0136]FIG. 53A is a graphical representation of two 6.42 μm red beadspositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0137]FIG. 53B is a series of signature traces derived from the beads ofFIG. 53A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0138]FIG. 54A is a graphical representation of two 6.33 μm polystyrenebeads positioned relative to the tracks of an optical bio-disc accordingto the present invention;

[0139]FIG. 54B is a series of signature traces derived from the beads ofFIG. 54A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0140]FIG. 55A is a graphical representation of a 5.5 μm glass beadpositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0141]FIG. 55B is a series of signature traces derived from the beadillustrated in FIG. 55A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0142]FIG. 56A is a graphical representation of a 4.5 μm magnetic beadpositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0143]FIG. 56B is a series of signature traces derived from the bead ofFIG. 56A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0144]FIG. 57A is a graphical representation of two 4.0 μm blue beadspositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0145]FIG. 57B is a series of signature traces derived from the beads ofFIG. 57A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0146]FIG. 58A is a graphical representation of a 2.986 μm polystyrenebead positioned relative to the tracks of an optical bio-disc accordingto the present invention;

[0147]FIG. 58B is a series of signature traces derived from the beadillustrated in FIG. 58A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0148]FIG. 59A is a graphical representation of two 2.9 μm white beadspositioned relative to the tracks of an optical bio-disc according tothe present invention;

[0149]FIG. 59B is a series of signature traces derived from the beads ofFIG. 59A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0150]FIG. 60A is a graphical representation of four 2.8 μm magneticbeads positioned relative to the tracks of an optical bio-disc accordingto the present invention;

[0151]FIG. 60B is a series of signature traces derived from the beads ofFIG. 60A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0152]FIG. 61A is a graphical representation of a mixture of beadsincluding 2.8 μm magnetic beads, 4.0 and 6.8 μm blue polystyrene beads,and different sized silica beads positioned relative to the tracks of anoptical bio-disc according to the present invention;

[0153]FIG. 61B is a series of signature traces derived from the clusterof beads illustrated in FIG. 61A, the traces being derived from an ACcoupled and buffered HF signal from the optical drive according to thepresent invention;

[0154]FIG. 62A is a graphical representation of two 2.9 μm whitefluorescent polystyrene beads positioned relative to the tracks of anoptical bio-disc according to the present invention;

[0155]FIG. 62B is a series of signature traces derived from the beads ofFIG. 62A utilizing a DC coupled and buffered HF signal from the opticaldrive according to the present invention;

[0156]FIG. 63A is a graphical representation of two 2.9 μm whitefluorescent polystyrene beads positioned relative to the tracks of anoptical bio-disc according to the present invention;

[0157]FIG. 63B is a series of signature traces derived from the beads ofFIG. 63A utilizing a DC coupled and buffered “A” signal from the opticaldrive according to the present invention;

[0158]FIGS. 64A and 64B are cross-sectional side views similar to FIG.51 showing the biochemical interaction between the bio-disc and thereporter beads in greater detail;

[0159]FIG. 65 is a cross-sectional side view of an optical bio-discincluding a proximally positioned red blood cell as the investigationalfeature interrogated by the read beam of the optical disc drive assemblyaccording to the present invention;

[0160]FIG. 66A is a graphical representation of a proximally positionedred blood cell approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to the present invention;

[0161]FIG. 66B is a series of signature traces derived from the redblood cell of FIG. 66A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0162]FIG. 67A is a graphical representation of a proximally positionedred blood cell approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to the present invention;

[0163]FIG. 67B is a series of signature traces derived from the redblood cell of FIG. 67A utilizing a DC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0164]FIG. 68 is a cross-sectional side view of an optical bio-discincluding a distally positioned red blood cell as the investigationalfeature interrogated by the read beam of the optical disc drive assemblyaccording to the present invention;

[0165]FIG. 69A is a graphical representation of two distally positionedred blood cells approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to the present invention;

[0166]FIG. 69B is a series of signature traces derived from the redblood cells of FIG. 69A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0167]FIG. 70A is a graphical representation of two distally positionedred blood cells approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to the present invention;

[0168]FIG. 70B is a series of signature traces derived from the redblood cells of FIG. 70A utilizing a DC coupled and buffered HF signalfrom the optical drive according to the present invention;

[0169]FIG. 71 is a perspective top view an optical inspection disc witha portion of the top cap cut away to illustrate a gnat's wing positionedin an inspection channel according to the present invention;

[0170]FIG. 71A is an enlarged top view of the indicated portion of FIG.71 showing in greater detail the gnat's wing, inspection channel,information storage tracks of the disc, and a focused spot of anincident beam on the tracks of the optical inspection disc according tothis embodiment of the present invention;

[0171]FIG. 72 is a cross-sectional side view taken perpendicular to aradius of the optical inspection disc of FIG. 71 including the gnat'swing as the investigational feature interrogated according to thepresent invention by the read beam of an optical disc drive assembly;

[0172]FIG. 73A is a graphical representation of a lateral section of thegnat's wing of FIGS. 71A and 72 as positioned in the inspection channelrelative to the tracks of an optical inspection disc according to thepresent invention;

[0173]FIG. 73B is a single signature trace derived from the section ofthe gnat's wing of FIG. 73A utilizing an AC coupled and buffered HFsignal from the optical drive according to the present invention;

[0174]FIG. 74A is a graphical representation similar to that shown inFIG. 73A;

[0175]FIG. 74B is a series of four consecutive signature traces derivedfrom the section of the gnat's wing of FIG. 74A utilizing an AC coupledand buffered HF signal from the optical drive according to the presentinvention;

[0176]FIG. 75A is a graphical representation similar to that shown inFIG. 73A;

[0177]FIG. 75B is a series of consecutive signature traces at moderatedensity derived from the section of the gnat's wing of FIG. 75Autilizing an AC coupled and buffered HF signal from the optical driveaccording to the present invention;

[0178]FIG. 76A is a graphical representation similar to that shown inFIG. 73A;

[0179]FIG. 76B is a series of consecutive signature traces at higherdensity derived from the section of the gnat's wing of FIG. 76Autilizing an AC coupled and buffered HF signal from the optical driveaccording to the present invention;

[0180]FIGS. 77A, 77B, and 77C are pictorial representations of thegnat's wing of FIGS. 71A and 72 as rendered by methods according to thepresent invention respectively utilizing either an AC coupled andbuffered HF signal, a DC coupled and buffered “A” signal, or a DCcoupled and buffered HF signal from an optical drive assembly;

[0181]FIG. 78 is a graphical representation illustrating therelationship between FIGS. 78A and 78B;

[0182]FIGS. 78A and 78B are electrical schematics of a second embodimentof the amplifier stages that may be implemented according to the presentinvention in the buffer cards shown in FIGS. 22 and 23;

[0183]FIGS. 79A, 79B, 79C, and 79D are cross-sectional side views of anoptical bio-disc showing a method of detecting investigational featuresin a test sample.

[0184]FIGS. 80A, 80B, 80C, and 80D are cross-sectional side views of anoptical bio-disc used in a mixed phase assay to detect investigationalfeatures in a test sample;

[0185]FIGS. 81A, 81B, 81C, 81D, 81E, and 81F are cross-sectional sideviews of an optical bio-disc showing a method of detectinginvestigational features in a test sample using ELISA;

[0186]FIG. 82 is a detailed partial cross-sectional view of the surfaceof a bio-disc showing reporter beads having specific affinity forantigens bound to the surface;

[0187]FIGS. 83A, 83B, 83C, and 83D are cross-sectional side views of anoptical bio-disc showing a method of using reporter beads to detectinvestigational features in a test sample;

[0188]FIG. 84 is a detailed partial cross-sectional view of the surfaceof a bio-disc showing use of reporter beads, capture probes, and signalprobes to detect investigational features in a test sample;

[0189]FIG. 85 is view similar to FIG. 84, showing hybridization of theinvestigational feature to the capture and signal probes; and

[0190]FIG. 86 is a cross-sectional side view of a bio-disc showing useof antibody-coated capture zones to detect analytes of interest in atest sample.

[0191]FIG. 87 is a schematic depiction of a technique that adds goodchannel bits to read out from an optical disk to facilitate thedetection of bio-bits.

[0192]FIG. 88A is a side view of a hybrid optical disc implementation.

[0193]FIG. 88B is a top view of a hybrid optical disc implementation.

[0194]FIG. 89A depicts a prior art implementation of the objectiveassembly in consumer CD-R player.

[0195]FIG. 89A depicts an implementation of the objective assembly in aCD-R player with an added adjustment lens.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0196] The present invention provides methods and an apparatus fordetecting operational and investigational structures or features on anoptical disc assembly without having to physically modify the processingcircuitry and using a conventional disc drive. According to oneembodiment of the present invention, one or more signal processingcircuits within the conventional disc drive is programmably configuredto function as an analog-to-digital (A/D) converter. The A/D converteris used to detect an electronic profile associated with investigationalfeatures and structures disposed on a surface of the optical discassembly. The profiles may be used to determine the relative size,composition, and location of the detected structures. Many differentsignals from the drive may be utilized to render the desired electronicprofiles. Different electronic signals available within the drive mayresult in different electronic profiles, perturbations, or “signatures”for the same investigational feature. It should be understood, however,that each such signature or signal perturbation is unique and thus maybe used as a separate and distinct indicator of the respectiveinvestigational feature under consideration. The conventional disc drivemay then be programmably returned to its original operatingconfiguration. Processing and imaging software both internal andexternal to the drive are discussed as related aspects of thisembodiment of the present invention.

[0197] In accordance with another embodiment of this invention, and asan alternative to programmably configuring one or more signal processingcircuits within the disc drive to function as an analog-to-digital (AND)converter, an external A/D converter with or without an external buffercard is employed. In these embodiments of the present invention, manydifferent signals from the drive may also be employed to render thedesired electronic profiles. As in the prior embodiment, differentelectronic signals available within the drive may result in differentelectronic profiles, signal perturbations, or “signatures” for the sameinvestigational feature. It is also understood relative to thisembodiment of the present invention, that each such signature is uniqueand thus may be used as a separate and distinct indicator of therespective investigational feature or attribute thereof underconsideration. Processing and imaging software are also related aspectsof this embodiment of the present invention.

[0198] The electrical characterization of light as it enters anobjective assembly of an optical disc drive can be utilized to createmulti-dimensional images of investigational features on an optical disc.An optical bio-disc can be designed to facilitate the gathering of dataand the creation of the image.

[0199] An optical disc drive may be utilized as an optical disc imagingdevice to produce multi-dimensional images from a signal element (i.e.,a specimen to be imaged) in an optical disc assembly. The energyreflected from the surface of an optical disc or optical disc assemblyis gathered on the photo detector in an objective assembly and utilizedto reproduce a multi-dimensional image. The optical disc properties(mechanical, logical, and optical) and the optical device properties maybe optimized to produce high-resolution multi-dimensional images that insome ways distinctly characterize the signal element.

[0200] The objective assembly and the optical detector of an opticaldisc drive can be adjusted to facilitate the collection ofhigh-resolution images of investigational features on the surface of anoptical disc. The quad detector inside the objective (or within theoptical path of the objective lens) is often organized as depicted by 18in FIG. 4.

[0201] With reference now to FIG. 8, chip set 30 of FIG. 4 can besupplemented relative to its original configuration by the addition oftap buffers 57, 58, and 59. These tap buffers provide access tounprocessed analog signals such as HF signal 50, TE signal 52, and FEsignal 54, respectively, produced by detector 18, thereby permittingexternal instrumentation to receive these signals without interferingwith normal drive operation.

[0202] An alternative modification is the addition of tap buffers toallow the unprocessed signals A though F from detector 18 to beprocessed by external instrumentation or additional circuitry. Fromthese signals, the HF, TE, FE, or any other combination can be formed.Also, any additional detectors available can provide useful signals inthis same manner (e.g., G and H detectors in current state-of-the-artdrives). Certain drive circuit designs and detector/amplifier devicesallow connection of the instrumentation or additional circuitry directlyto the detector without the need for the tap buffers.

[0203] Referring next to FIG. 9, there is shown an optical disc drive140 according to the present invention. Optical disc drive 140 has disctray 168, which is adapted to receive a disc 130 of a type designed toaccommodate a wide variety of investigational features. Disc 130 may bean optical bio-disc such as those disclosed in commonly assigned U.S.Provisional Application Nos. 60/252,726 entitled “Bioactive Solid Phasefor Specific Cell Capture and Optical Bio-Disc Including Same”;60/249,391 entitled “Optical Disc Assembly for Performing Microscopy andSpectroscopy Using Optical Disc Drive”; and 60/257,705 entitled “SurfaceAssembly for Immobilizing DNA Capture Probes and Bead-Based AssayIncluding Optical Bio-Discs and Methods Relating Thereto.”

[0204] Known optical disc drives are often packaged within a case thatincludes both the optical disc drive 140 and one or more processingcircuit boards as discussed herein. The basic optical disc drive (e.g.,optical disc drive 140) provides a variety of signals derived from theoptical disc. For example, most optical disc drives provide an HF signal50 as a basic information signal. Such drives also provide a trackingerror signal (TE signal) 52, a focus error signal (FE signal) 54, andbasic signals from the sensing or laser photo detectors often referredto simply as the A, B, C, D, E, and F signals. In a known type ofoptical disc drive, these signals are processed in a processing circuitboard to provide any correcting signals that may be needed to operatethe optical disc drive or derive information signals from the opticaldisc. Such a processing circuit board is frequently packaged within theoptical disc drive and may include, for example, a programmable signalprocessor, as discussed herein.

[0205]FIG. 9A shows five implementations of the present invention. Theseare identified as implementations I, II, III, IV, and V, respectively asillustrated. It should be understood that each implementation might haveseveral embodiments, all of which accomplish the objects of the presentinvention.

[0206] In an embodiment of implementation V of the present invention,the unprocessed HF signal 50 is tapped from the optical disc drive 140and directed to a modified personal computer or PC 142. Persons skilledin the art will appreciate in light of these teachings that modified PC142 may be any suitably adapted and programmed processor,microprocessor, application specific integrated circuit (ASIC) or thelike. The modified PC 142 includes software and hardware for processingthe HF signal generated from the read beam of the optical drive 140which is modulated as a function of encountering one or moreinvestigational features on or in any one or more of a number ofdifferent layers, substrates, or surfaces forming disc 130. The sameread beam is also modulated in a conventional manner by encountering orreading operational features in disc 130. Such operational featurestypically include pits and lands as in a pre-recorded CD-like disc ormarks and spaces formed by dyed and undyed areas in a recordable discsuch as a CD-R. The pits and lands, or marks and spaces, embody encodedinformation in the nature of data, program, video, and/or audioaccording to any one of a number of schemes for encoding suchinformation.

[0207] With modified PC 142, the optical disc drive 140 preferablyincludes a buffer amplifier (not shown for clarity) to provide anamplified replica of the HF signal so that the actual HF signal is notdistorted by being excessively loaded. The amplified replica of the HFsignal (or the actual HF signal itself, if need be) is coupled tomodified PC 142 by a cable. The software and hardware for processing theHF signal in the modified PC 142 includes an analog-to-digital converter(ADC) as part of modified PC 142, preferably a data acquisition board ormodule that includes a suitable ADC (e.g., with sample rates from 8 MHzto 40 MHz). The ADC digitized sampled data is stored in the PC's RAM,and processed by the PC under control of the PC's software.

[0208] Modified PC 142 may advantageously include a keyboard 144, amonitor 146, and speakers 148. After the modified PC 142 processes theraw HF signal in a desired manner, characteristic aspects of theinvestigational feature (as discussed below) may be displayed on themonitor 146. The monitor 146 and speakers 148 may also be employed todisplay conventional video or audio encoded on disc 130. ImplementationV of the present invention will be hereinafter referred to as the“modified PC implementation” for purposes of convenience and clarity.

[0209] In an embodiment of implementation III of the present inventionillustrated in FIG. 9A, the optical disc drive 140 is packaged with aprocessing circuit board that includes a programmable DSP 32 (similar tothe DSP in FIG. 8) and an analyzer 154 that operates in combination witha PC 158. PC 158 includes software, and hardware controlled by thesoftware, implemented to accommodate analysis of investigationalfeatures. Analyzer 154 may include another programmable DSP, aprogrammable microprocessor, application specific integrated circuit(ASIC) or the like implemented to perform functions in support of abiological, chemical, or biochemical investigation. Programmable DSP 32includes an ADC to digitize the HF signal (or other signal). Analyzer154 may simply provide a count of the number of times a voltage levelexceeds a threshold. Alternatively, analyzer 154 may identify voltagevariations (e.g., double peaks, etc.) or other waveforms that arecharacteristic of investigational features. In any event, programmableDSP 32 performs the highest bandwidth functions, PC 158 performs thelowest bandwidth functions, and analyzer 154 performs functions ofintermediate bandwidth. Persons skilled in the art will appreciate inlight of these teachings that functions of analyzer 154 may be subsumedinto the capabilities of programmable DSP 32, PC 158 or both. Personsskilled in the art will also appreciate in light of these teachings thatPC 158 may be any suitably adapted and programmed processor,microprocessor, application specific integrated circuit (ASIC) or thelike. Aspects of this alternative implementation are described infurther detail herein below. For purposes of convenience and clarity,implementation III of the present invention will hereinafter be referredto as the “DSP implementation.”

[0210] According to an embodiment of implementation I of this invention,a tap-off of the HF signal, as buffered by the tap buffer 57 shown inFIG. 8, from drive 140 may be directed to an external analog-to-digitalconverter 150 (ADC 150) as shown in FIG. 9A. As with the modified PCembodiment, the optical disc drive 140 preferably includes bufferamplifier 152 to provide an amplified replica of the actual HF signal sothat the actual HF signal is not distorted by being excessively loaded.The amplified replica of the actual HF signal (or the HF signal itself,if need be) is coupled to ADC 150. Alternatively, any one of a varietyof different signals or signal combinations (e.g., the TE and FE signalsor the A, B, C, D, E and F signals) may be tapped off of the drive 140as illustrated. Aspects of this alternative implementation are alsodescribed in further detail herein below. For purposes of convenienceand clarity, this embodiment of the present invention will hereinafterbe referred to as the “A to D embodiment” of implementation 1. The A toD embodiment may be modified to include external buffer amplifier card152 illustrated as implementation 11 in FIG. 9A.

[0211] With continuing reference to FIG. 9A, implementation IV of thepresent invention illustrates that the audio output of the optical discdrive 140 (i.e., the audio signal) may be utilized, modified, oraugmented to produce a sound when the interrogation beam of the driveencounters an investigational feature or attribute. For example, a discmay be pre-recorded with digital silence yet a sound is produced whenthe read beam “reads” or detects an investigational feature. In thismanner, different investigational features may produce discerniblydifferent sounds or tones. Alternatively, the disc may include a soundtrack that would be interrupted by the formation or presence of aninvestigational feature blocking the encoded sound information. Theseembodiments of the present invention may be generally grouped into threedifferent categories, approaches, or techniques. The first includesusing the existing sound card that is currently available and usuallypackaged in many drive assemblies, for example, an audio CD player. Sucha sound card generally produces an analog sound signal, but may alsogive access to a digital signal representative of the sound. The secondapproach is directed to internally modifying the audio circuitry thatexists in such current drive assemblies to provide the analog or digitalsignal. The third alternative approach or technique according to thepresent invention, is to provide an external sound module (depicted asaudio processing 156 in FIG. 9A) that interfaces with the disc driveassembly 140, processing software, and an audio output device such asthe pair of speakers 148. Implementation IV of the present may generallybe referred to as the “audio” implementation.

[0212] All of the different implementations illustrated in FIG. 9A,except the modified PC implementation (V), would typically include aconventional PC 158 for functionality described in further detail below.The modified PC implementation would inherently include a PC, and wouldbe modified as to its inputs. However, persons skilled in the art willappreciate in light of these teachings that PC 158 may be any suitablyadapted and programmed processor, microprocessor, application specificintegrated circuit (ASIC) or the like.

[0213] Commonly assigned U.S. patent application Ser. No. 09/421,870entitled “Trackable Optical Discs with Concurrently Readable AnalyticMaterial” (hereinafter the '870 application) discloses coupling anoscilloscope to the HF or RF signal for detecting the dual peak profilesassociated with investigational structures while acquiring the encodedinformation needed to operate the disc drive. These peaks appear as aresult of changes in reflectance as the light beam traversesinvestigational structures or reporters on the optical disc surface.Such electronic profiles may be advantageously used to detect anddiscriminate among structures under investigation.

[0214] An embodiment of implementation 11 shows an analog-to-digital(A/D) converter 150 (ADC) connected to the HF signal through buffer 152.Implementation II may, for example, determine the number of dual peaksencountered (and thus the number of investigational structures orreporters) on any portion of the optical disc. ADC 150 forms digitizedsamples of the analog HF signal (or other suitable signal), and formsthe samples at a sample rate fast enough to capture the characteristicsof the peak profiles that are associated with the investigationalstructure. The magnitude and/or duration of the digitized peak signalsmay be interpreted by an associated application program to determine therelative size, composition, and location of the detected structures.

[0215] Operational Functions

[0216] Light gathered, reflected, or generated from operational featureson disc 130 (FIGS. 9A and 12) and processed by components in objectiveassembly 10 (FIG. 1) are projected onto detector 18 and createelectrical signals that are used by servo circuitry 34 (FIG. 6) toprovide operational function to the drive. These patterns provideinformation that allows objective assembly 10 to focus above a focalplane in disc 130 and track operational features (e.g., pits, grooves,lands) that allow objective assembly 10 to be moved along theinformation tracks associated with the operational surface of the discassembly.

[0217] The operational functions of a drive and the signal that directsthe drive to perform those operational functions may be utilized toreproduce a multi-dimensional image. These operational functionsinclude, but are not limited to, focusing, tracking, andsynchronization. The sum of all of the energy reflected and/or createdfrom the interaction of the signal element with the light emitted fromthe objective assembly is often referred to as the HF (high frequency)or RF signal. If the photo detector in the objective assembly isorganized in a quadrant (as depicted by 18 in FIG. 4), then the signalis referred to as the quad sum signal. This summed signal contains mostof the information necessary to reproduce the image through algorithmicmanipulation. The other components of the photo detector will producesignals that may be independently measured to produce additionalinformation or operational signals. For example, the energy gathered inthe quad detector of an optical disc drive may be organized to produceoperational functions as follows:

A+B+C+D=HF or Quad Sum (provides sync. for pits)

A+D−(B+C)=Tracking (push-pull technique) (sync. for grooves)

A+C−(B+D)=Focusing (astigmatic technique)

E−F=Tracking (outrigger technique)

[0218] These photo detector component signals may be used independentlyor in any combination to produce characteristic information about thesignal element or signal elements. In most embodiments an algorithmicinteraction is necessary in software to reproduce characteristicimaging. The quad detector is the most common in the current market,however a detector distribution that contains more than 4 to 6components may also be used to enhance characterization. Also, theoptical path may be configured in the device to provide signalcharacterization with coherent, partially coherent, or non-coherentlight.

[0219] Signal responses may be gathered directly or indirectly from theoperational signals in the optical disc drive. In one embodiment of theimaging aspects of this invention, an operational signal is directlyamplified, digitized, or sampled (bit resolution, sampling rate) andthen algorithmically adjusted through software to produce acharacteristic image of the signal element. The operational signals mayalso be electrically manipulated before or after they are digitized. Anoperational signal may be filtered, amplified, or summed with anothersignal component before it is digitized in order to produce acharacteristic, non-random, or correlative response. For example, asignal may be measured or characterized by an external electricalmanipulation such as a signal analyzer. A signal may show a non-random,correlated event when its response is filtered, amplified, ormathematically combined with other signals (e.g., asymmetry, push pull,cross-talk, radial noise, etc.).

[0220] Signals produced from investigational or non-operational featuresmay also be utilized independently or in combination to producecharacteristic images of the investigational feature under study. Thesignal and logical responses produced by the optical disc drive may alsobe used to reproduce a characteristic of a signal element orinvestigational feature. This is somewhat different than the utilizationof the signals performing the necessary operational characteristics. Adigital signal, analog signal, logical response, optical response, ormechanical response may be gathered from an optical disc drive tocharacterize the signal element or investigational feature. For example,a signal element with a specific optical or physical property willinteract with light in such a way that a characteristic energy patternor energy distribution is created. This characteristic distribution orpattern on the photo detector may be monitored and measured as aresponse without adversely affecting the operational functions of thedrive.

[0221] In one exemplary embodiment, an objective assembly in an opticaldisc drive will interface with the operational features on a surface ofan optical disc assembly. This interaction may include the support ofall of the operational functions or it may include the suspension of oneor more of the operational functions in a predefined “Zone” of the disc.The interaction of the incident beam from the objective assembly withthe operational surface and investigational features will produce signalresponses in the HF signal, the tracking signal, and the focusingsignal. The focusing signal including operational information andinformation about characteristics of an investigational feature, may beused with an electrical servo circuit to support a response to themovement of the objective assembly within a direction that we will referto as the “Z” direction, as shown in FIG. 9B. The tracking or push-pullsignal may be used with an electrical servo circuit to support aresponse to the movement of the objective assembly in a direction thatwe will refer to as the “X” direction illustrated in FIG. 9B. The HFsignal, DPD signal, or quad sum components may be used to support aresponse to the movement of the objective assembly in a direction thatwe will refer to as the “Y” direction. In this way we can gather a3-dimensional (XYZ) response from the interaction of the incident beamwith a signal element or investigational feature 136 by using standardoperational responses of the objective assembly.

[0222] The signal element or investigational feature 136 covers an areain the disc that interacts directly or indirectly with an operationalfeature that provides a tracking signal. The signal element may bedistal relative to the operational features such as, for example, in atransmissive or semi-reflective disc as described below in furtherdetail. Alternatively, the signal element may be removed from areashaving full operational functionality such as in a separate “Zone” or“mirror band” formed in or on the disc wherein at least some of theoperational functionality has been removed. The signal element may be ona focal plane that is physically removed from an interference patternproducing other operational signals (focus and/or tracking and/or sync.)The signal element should provide a measurable contrast or energydistribution. This contrast may be provided by the difference betweenthe reflective properties of the operational structure (focal plane) andthe reflective properties of the signal element.

[0223] The signal element or investigational feature may be lessreflective than the operational plane thus providing a decreasing energysum to the photo detector. The signal element may have the same orsimilar reflective properties as the operational plane (or focal plane)but provide a diffractive or phase cancellation, or phase enhancement,response that provides a decreasing signal level in the photo detector.The signal element may be more reflective than the operational planethus providing an increasing signal level in the photo detector sumsignal. The design of the optical disc drive and the design of theoptical disc assembly operational features may be enhanced to optimizeimaging capabilities.

[0224] The operational plane that provides a focal plane can be designedto provide maximum contrast or enhancement to the laser/signal elementinteraction. As would be understood by one of ordinary skill in the art,focal plane includes the point of greatest reflectively at anyparticular time during laser focusing. If the focal plane is morereflective than the signal element or investigational feature, then itis desirable to enhance the interference or phase contrastcharacteristics of the design. If the focal plane is less reflectivethan the signal element, then it is desirable to enhance thereflectivity and linear signal response of the signal. The focalresolution is dependent on the wavelength of the laser in the objectiveassembly, the numerical aperture of the focal lens, the bandwidth of thefocusing servo loop, and the optical properties of the optical discassembly.

[0225] In the design of the disc system according to the presentinvention, it is important to create strong signal recognition patternsthat differentiate operational function from signal elementcharacterization. The light reflected, absorbed, or transmitted throughthe disc should characterize the signal element with as much detail andmagnitude as possible.

[0226] The response in the reflected or transmitted light can beinfluenced by the signal element in many ways. The signal element itselfcan also be designed with the operational characteristics of the disc toprovide a high degree of contrast in the transmitted or reflected light.The energy level, energy distribution, and polarization state of thelight can be influenced by the design of the signal element and itsrelationship to the optical properties of the focal plane in the disc.

[0227] One embodiment directed to signal element selection and design,is to create a signal element that has a reflectivity that is vastlydifferent from the reflectivity of the focal plane of the disc. Thereflectivity of the signal element is thus designed to be very high orvery low in comparison to the reflectivity of the disc. This willproduce a high amount of signal contrast and a strong characteristicsignal.

[0228] The difference in reflectivity between the focal plane and thesignal element can be generated in many ways. These include, but are notlimited to, the following:

[0229] 1. The material in the signal element can have a lower or higherreflectivity and thus produce a lower or higher signal level than thesurrounding plane of the disc.

[0230] 2. If the signal element is smaller than the beam size, aninterference pattern is created and the size of the signal element cancreate a destructive or additive component to the signal.

[0231] 3. The signal element may be activated by an energy source thatcreates a state condition that results in a lower or higher reflectivitythan the surrounding area (phase change materials).

[0232] An alternative embodiment directed to signal element selectionand design involves the use of materials and states that interfere withthe polarization state of the light transmitted or reflected through thedisc. The signal element can be designed to have an optical or magneticproperty that has a contrasting effect on the polarization state of thelight interacting with the disc assembly. There are many ways that thisembodiment can be created in the disc. These include, but are notlimited to, the following:

[0233] 1. A signal element can be designed that is transparent butbirefringent or diChroic in nature. The optical components of thedetector will transmit, reflect, or absorb the resulting signal based onits state.

[0234] 2. A signal element may be designed to produce a magneticorientation that provides a contrasting polarization state in the light.

[0235] A third group of embodiments directed to signal element selectionand design involves the use of optical or interference properties thatinterfere with the energy distribution of light that is transmitted orreflected through the disc. The signal element can be designed todiffract the light in such a way that it creates a higher energyresponse from a non-intrinsic detector. A measurable or detectablecontrast is provided in the resulting signal by the area of light on thesurface of the detector.

[0236] A fourth group of embodiments directed to signal elementselection and design involves the use of chemical luminescence. Thesignal element or surface of the disc can be designed to emit energy ina secondary active state. This involves, for example, the use offluorescent or phosphorescent markers or dyes applied to the signalelement and/or an appropriate disc surface. Suitable signal elements forthis group of embodiments include, but are not limited to, beads andcells such as blood cells, for example. The state is activated by theincident energy on the disc assembly. A contrasting energy is therebycreated and exists in the transmitted or reflected return signal.

[0237] The present invention is thus directed to an optical analysisdisc for detection of a signal element. The disc preferably includes asubstrate layer and an operational layer associated with the substratelayer. The operational layer has operational information encodedtherein. According to this aspect of the present invention, the analysisdisc further includes a signal element positioned relative to theoperational layer. The signal element and the operational layer haveoptical or magnetic characteristics selected to provide a predeterminedcontrast therebetween to thereby provide a return signal indicative ofdistinctions between information associated with the operation layer andcharacteristics of the signal element.

[0238] Incident Light

[0239] The wavelength of light emitted by laser (i.e., light source 19FIGS. 1 and 12) utilized in objective assembly 10, FIG. 1, of theoptical disc drive will have an effect on the resolution of the opticaldisc system. In theory, the smallest signal element or investigationalfeature that may be detected by an objective assembly (at theelement/laser interface) with a wavelength λ will be λ/2NA, where NA isthe numerical aperture of the objective lens. At any instant in time,the investigational feature or signal element, at the laser/planeinterface may be larger or smaller than the field that is covered by thebeam at or near the focal point. A signal element that is larger thanthe laser beam coverage at the laser/signal element interface willproduce more characteristic signals than a signal element that issmaller than the laser coverage.

[0240] The wavelength of the laser should be as small as possible toenhance the resolution of the signal response. This will result ingreater detail and characterization capabilities for smaller signalelements and investigational features. Shorter wavelengths producesmaller focal spots on the focal plane of the optical disc assembly.Therefore, a shorter wavelength will produce a higher spatial resolutionin the imaging device. An objective assembly with a high numericalaperture will provide less focal distance and greater diffractioncapability.

[0241] The drive should have very little mechanical or electricalinfluence on the signal response or signal consistency of thelaser/signal element interface. In certain circumstances, the driveoperation may have an influence if designed to do so (e.g., electricalcoupling, sync enhancement, signal gain control settings AGC, signalpower level setting).

[0242] Extracting Information from an Optical Disc

[0243] Referring now to FIG. 10, the conventional process of encodingvideo, data, or audio information such as music on a disc and then laterdecoding signals from the disc to recover the audio, video, or data isillustrated. The audio, video, or data signal is sampled at block 70,quantized at block 71, encoded into a standard format at block 72, andmodulated onto a master disc at block 73. Replicated discs are then massmanufactured at block 74. In a disc reader, signals derived from amanufactured disc are processed through a signal processor at block 75,demodulated at block 76, then decoded at block 77 to recover theoriginal audio, video, and/or data. This output is then displayed on amonitor and/or played on a pair of speakers for a user's use andenjoyment.

[0244] With reference next to FIG. 11, an optical disc decoding systemis shown modified in such a way that some functionality in the system isremoved. The path is modified to remove the Demodulation and Decodingoperations (blocks 76 and 77 of FIG. 10) and provide a raw digitizedsignal to a computer to effectively characterize a group of signalelements of investigational features on a surface of the optical discassembly.

[0245] In addition to pre-recorded optical discs, a variety ofrecordable optical discs are currently available. A recordable masterincludes a variety of operational features that are designed for useduring the recording operation and not the reading operation. Table 1below summarizes these operational differences. TABLE 1 Reading orRecording Playback Disc Type Function Properties Properties CD-R FocusSurface Properties Surface CD-RW Properties Tracking 22.05 KHz WobblePits or Marks Groove Synchronization 22.05 KHz Wobble Pit Patterns(speed control) Groove (Marks) DVD-R Focus Surface Properties SurfaceDVD-RW Properties DVD-RAM Tracking 140 or 160 KHz Pits or Marks DVD + RWWobble Groove Synchronization 140 or 160 KHz Pit Patterns (speedcontrol) Wobble Groove (Marks)

[0246] As indicated above, the decoder or servo system of a CD, CD-R, orDVD player can be used to provide a count, correlation, orcharacterization of a chemical response in the focal or operationalfeature plane of a disc. Other responses or raw signals from the drivechip set that quantify the signal magnitudes from an investigationalfeature or signal producing element include the high frequency signal(HF) (AC or DC coupled), the tracking error signal (TE), the focus errorsignal (FE), the Automatic Gain Control Setting (AGC), the push-pulltracking signal ((B+C)−(A+D)), the CD tracking signal (E−F), the CD-Rtracking signal ((A+D)−(B+C)), the focus signal ((A+C)−(B+D)), thedifferential phase detector signal (DPD) ((A+B)−(C+D)), the powermonitor signal from the back of the laser, and the audio signal.Additional signals, which may be employed with the present invention,include the individual signals from the quad detector, A, B, C, and D,or side detectors E and F.

[0247] A trend in current conventional drives is to use a high-densityphoto detector array in place of the typical quad detector. The methodsof the present invention may also be advantageously utilized inconjunction with such array detectors currently becoming available inthe market. These arrays include, for example, individual signals A, B,C, D, E, F, G, . . . Z. Each of these signals, or combinations thereof,may be advantageously employed according to different embodiments ofthis invention to obtain the desired electronic profiles, signatures, orsignal perturbations that uniquely characterize the signal element,investigational feature, or attribute of interest.

[0248] Imaging Techniques and Operational Features

[0249] The operational features and layout of the optical bio-discassembly can be designed to optimize the imaging operation. The opticaldisc assembly may be further designed in specific areas or “zones” toenhance the detection and characterization of signal elements orinvestigational features and to provide higher signal resolution withspecific laser interface properties.

[0250] The operational features most often provide tracking signals thatallow the objective assembly to move from the inner to the outer area ofthe optical disc assembly. A smaller track pitch, or spacing between theoperational features, will yield a greater resolution because of thecorresponding increase in the number of responses associated with theinvestigational feature. By providing an operational feature that issmaller than the signal element and a track pitch that is comparable tothe signal element, multiple electrical scans can be gathered from thelaser/signal element interaction. The number of potential scans of asignal element at a fixed position on or near the operational plane(focal plane) is increased as the track pitch is decreased. The accuracywith which the location or position of the investigational feature orsignal element on the disc can be resolved, is increased as theoperational features are made smaller given a fixed signal element size.This location accuracy is herein generally referred to as “positionalresolution”. This holds true with a consistent objectiveassembly/operational feature interface. The typical track pitch for a CDis 1.5-1.7 μm, for a DVD is 0.73-0.75 μm, and for a DVD-RAM is 0.35 μm.

[0251] The operational features also provide synchronization informationthat affects the speed of rotation of the disc and thus the durationduring which the laser interacts with the signal element. Lower speedsproduce higher quantized resolution in the digitization of the signal bythe A/D converter. This increases the sampling resolution of the system.As the rotational speed is increased, the sampling frequency and bitresolution must be increased in a corresponding manner to achieve aconsistent sampling resolution. The typical track speed for a CD is 1.2m/sec, and for a DVD is 3.49 m/sec.

[0252] The optical disc assembly or a section of the optical discassembly may be designed specifically for imaging. A disc with a slowrotational speed, a tight track pitch, and an optimized focal plane willprovide an exceptional response for imaging purposes. An optimal disc ordisc component design would also include logic to provide random accessto preaddressed investigational locations of positions on the disc. Thelogic may be encoded in the operational features of the disc oralternatively formed by physical markings on the disc assembly. Thelogic may be designed to accommodate the investigational protocols forspecific assays assigned to different zones on the disc. Suchinvestigational protocols include, but are not limited to, samplingrate, bit resolution, rotational speed, focus and tracking off-set,laser power, laser light wavelength, rotational direction, acceleration,deceleration, and any other system interactions required by a particularassay.

[0253] An optical disc system can be created with (1) operationalfeatures or tracking features having a very tight track pitch tofacilitate the tangential resolution of the data gathered (e.g.,DVD-0.74 μm); (2) logic and hardware that provide for land/groove orland/pit tracking, enhancing the tangential resolution (e.g., DVD-RAM orMO); (3) logic or operational features that provide for slower discrevolution speed (shorter pits or wobbled grooves) to provide highersignal detail; (4) disc or lens component thickness' that may be made topromote a smaller or larger spot on the focal plane of the disc assembly(the components to be imaged may be slightly out of the exact focalplane or they may provide a new focal position for the objectiveassembly); (5) hardware providing a lower wavelength laser to enhanceresolution (e.g., DVD 635-650 nm, HD-DVD approximately 400 nm); (6) asampling system that provides a higher sampling frequency or highersample bit resolution to enhance the imaging; (7) software to providethe processing functionality of mathematical transforms or operationalfunctions to derive approximations to the imaging; and (8) the disc orlens component positioned laser proximal to the feature that enhancesthe interaction of the light with the feature (e.g., an SIL-typecomponent for manipulating the evanescent field).

[0254] In the imaging of an investigational feature as situated on anoptical bio-disc, it is desired to produce any measurable contrastbetween the investigational feature or signal element and the focalplane. This desired contrast can be achieved by use of reflective signalelements or investigational features in combination with a lessreflective focal or operational plane. Alternatively, the desiredcontrast can also be achieved by use of non-reflective signal elementsor investigational features in combination with a more reflective focalor operational plane.

[0255] Optical Disc Drive and Related Disc Formats

[0256] The optical bio-disc may be implemented on an optical discincluding a format such as CD, CD-R, or DVD or a modified versionthereof. The bio-disc may include encoded information for performing,controlling, and post-processing the test or assay. For example, suchencoded information may be directed to controlling the rotation rate ofthe disc. Depending on the test, assay, or investigational protocol, therotation rate may be variable with intervening or consecutive sessionsof acceleration, constant speed, and deceleration. These sessions may beclosely controlled both as to speed, direction, and time of rotation toprovide, for example, predetermined mixing, agitation, or separation offluids and suspensions with agents, reagents, or antibodies. A discdrive assembly is employed to rotate the disc, read and process anyencoded information stored on the disc, and analyze the liquid,chemical, biological, or biochemical component in any assay zone of thedisc. The disc drive assembly may also be utilized to write informationto the bio-disc. The recording may occur either before or afterperforming the assay or test.

[0257] According to another embodiment of the present invention, anoptical disc drive chip set is employed as an A/D converter to sample aread beam and thereafter to identify investigational features andstructures, and thereafter to characterize such features and structuresas unique signal perturbations or electronic signatures. An optical discdecoding system may be modified in such a way that some functionality inthe system is removed. The removal of specific features from thedecoding path of an optical disc decoder will provide a raw digitalsignal that effectively characterizes and uniquely identifiesinvestigational features positioned on the surface of the opticalbio-disc, on a substrate within the disc, or residing within a chamberor channel formed as a fluidic element of the disc assembly.

[0258] According to another embodiment of the present invention, aconventional disc drive is employed to identify investigational featuresand structures. In this case, firmware modifications enable the user tomonitor known signals within the disc drive, without the need to modifythe electronics or hardware. The value of the AGC signal can be usefulas a measuring tool. The AGC functionality tries to ensure that theanalog output signal has a consistent range. If the disc drive is usedto read binary data, only a high value and a low value are needed. Inthe case of investigational features, however, values may be desirableover a continuum of ranges. The AGC is high where the signal level islow, and vice versa. The AGC can thus be used as a signal that isrepresentative of the light that is received by the detector, andtherefore can be used for measurement and detecting changes in aninvestigational feature.

[0259] A CD-R player/recorder of this embodiment adds an adjustment lensto the objective assembly of a commercial optical disc player. Aplayer/recorder that is designed for use in the consumer market for therecording of recordable CD discs can be utilized to detect microscopicstructures. The drive is modified at the exit position of the objectiveassembly. A small refractive optical lens is added to the optical pathof a CD-Recordable drive. FIGS. 89A and 89B show the addition of thisadjustment lens. FIG. 89A shows a commercial optical disc player withrecordable CD disc 1112. The shaded area indicates a 1.2 mmpolycarbonate layer that helps focus and polarize the beams. In FIG.89B, an adjustment lens 1114 is added at the exit position of theobjective assembly 1110. This optical adjustment lens provides thenecessary focusing and polarization characteristics to provide forstandard operation of the CD-Recordable drive. The adjustment lens willadjust the focusing path and provide the necessary reflection to thediode laser to provide the desired spot size and energy distribution onthe surface of the optical disc. The adjustment lens will provide apolarizing phase shift similar to the polarizing shift provided by the1.2 mm polycarbonate layer in the construction of the optical disc. Thislayer is absence in the disc 1116 used in the present embodiment.Instead an air-filled layer is used for depositing biological samplesfor detection and analysis. The characteristics of the adjustment lenscan be changed to provide an optimal situation for the detection ofbio-bits such as beads, cells, colloidal gold, carbon, or othermicroscopic markers and reporters associated with an optical disc. Theadjustment lens is designed in such a way as to optimize the operationalcharacteristics of each component in the optical path of an optical discplayer/recorder.

[0260] A sampling system is designed and optimized to detect andcharacterize the electrical responses from the investigationalstructures and signal elements on the surface of the optical analysisdisc. The sampling system monitors and delivers information from theservo control signals discussed previously. The information deliveredwill include qualitative and quantitative information.

[0261] The objective assembly of an optical disc player or recorder willsend out a modulated or continuous wave laser pulse from a laser diode.It will record the reflected information from the surface of an opticaldisc on a combination photo detector and will generate four servosignals that provide for the operational requirements (i.e., tracking,focusing, synchronization, and power control). The microscopicstructures can be detected and characterized from each, or acombination, of the electrical signals that are generated from theelectrical servos. This includes, but is not limited to, the use of alltracking spots on a 3-beam outrigger system to detect and characterizefeatures.

[0262] The focusing servo signal may be generated from at least 3focusing techniques: critical angle focusing, Focault or knife-edgefocusing, or astigmatic focusing. The tracking servo signal may begenerated from at least 4 types of tracking techniques: one beampush-pull tracking, 3 beam outrigger tracking, Differential PhaseDetection (DVD), or one beam high frequency wobble tracking.Synchronization is generated from at least three differing methods: bitclock synchronization or bit pattern sync, zoned clocking method(DVD-RAM), or wobbling groove synchronization. Power control isgenerated from more than 4 methods: power monitoring signal in PCA orCD-R disc, running power control method or real time power control ofpulse diode, power or strategy adjustment, or optimum power encoded inwobble groove information. Logic is generated from over 40 known opticaldisc formats. Logic can perform position sensing, power control, radialand tangential location, layer sensing, density detection, multi-sessionusage as well as a wide variety of other functions.

[0263] The optical disc drive servos can be used to detect sizes ofinvestigational features, signal elements, or various structuresthereof. The movement of the laser across the bio-bit will result in asignal deflection in the optical disc tracking system servo signaland/or the optical disc focus system servo signal. The deflection in theelectrical signal associated with a closed loop signal beam push-pulltracking system or 3-beam outrigger tracking system is used tocharacterize the bio-bit and can be processed as a quantifiable piece ofdigital or analog information. The deflection in the electrical signalassociated with a closed loop 3-beam astigmatic or closed loop 1-beamFocault focusing system can be used to characterize the bio-bit and canbe processed as a quantifiable piece of analog or digital information.

[0264] As the push-pull tracking system interacts with a sphericalbio-bit, the optical assembly is moved in both the horizontal andvertical planes. The movement of the optical assembly in the horizontalplane will be toward the outer or inner radial direction. This willresult in a positive or negative deflection of the electrical signalapplied to the push pull tracking servo circuit. A low pass or band passelectrical filter may be used to determine the presence andcharacteristics of the bio-bit.

[0265] As the 3-beam outrigger tracking system interacts with aspherical bio-bit, the optical assembly will be moved in both thehorizontal and vertical planes. The movements of the optical assembly inthe horizontal plane will be toward the outer or inner radial direction.This will result in a positive or negative deflection or the electricalsignal applied to the differential tracking servo circuit. A low pass orband pass electrical filter may be used to determine the presence andcharacteristics of the bio-bit.

[0266] An electrical circuit that is electrically isolated from thetracking servo loop can determine differences in the characteristics ofthe bio-bits. This electrical circuit may be a series of low pass orband pass filters that are used to isolate and characterize thefrequency and magnitude of the deflections in the closed loop trackingsystem that are caused by the movement of the laser over the bio-bits.The size of the bio-bits can be characterized by the magnitude ofdeflection of the electrical tracking signal in the push-pull trackingsystem or the outrigger differential tracking system. The size and shapeof the bio-bits may also be characterized by the frequency of thedeflection of the electrical tracking signal in the push-pull ordifferential tracking system.

[0267] In other embodiments of the present invention, an optical discassembly with multiple beams read from a disc with multiple layers. Onelayer/beam pair provides the operational elements such as tracking. Atthe same time the remaining layer/beam pairs are used for detectingbio-bits.

[0268] Controlling Drive Functions

[0269] In order for the optical disc system to correctly operate itmust: (1) accurately focus above the operational plane of the opticaldisc assembly; (2) accurately follow the spiral disc track or utilizesome form of uniform radial movement across the disc surface; (3)recover enough information to facilitate a form of speed control (CAV,CLV, or VBR); (4) maintain the proper power control by logicalinformation gathered from the disc or by signal patterns detected in theoperational plane of the disc; and (5) respond to logic information thatis used to control the position of the objective assembly, speed ofrotation, or focusing position of the laser responsible for providingoperational requirements.

[0270] An optical disc objective assembly performs three principaloperational requirements by utilizing electrical and logical servos. Anobjective assembly thus provides an electrical signal to: (1) thefocusing servo circuitry, (2) the tracking servo circuitry, and (3) theinformation processing circuitry. In the case of a CD recordable system,a fourth requirement is necessary to provide power control. In thesesystems, the objective assembly also provides an electrical signal tothe laser power control circuitry (“Signal Monitor”).

[0271] When a CD-Recordable (CD-R) disc is played back on aCD-Recordable player, it utilizes a “continuous wobbled groove” and areflective disc surface to provide information to the focusing servo,tracking servo, and power control servo. No features are detected on thesurface of the optical disc until a recordable disc is written andcontrasting marks have been provided. The quad sum detector will detectlight-contrasting structures that are placed on the air-incident surfaceof a reverse imaged CD recordable disc. These structures will providecharacteristic signals that can be detected by electrical monitoring ofthe quad sum detector.

[0272] The wobble signal is used to satisfy operational requirements #2and #3 above. There is a component of the wobble signal referred to assecondary wobble (Bi-phase mark) that is responsible for operationalrequirement #5.

[0273] The pit or mark patterns are detectable in both the tracking andHF signals of the optical objective assembly. No signals are generatedin the radial plane. By using the CD recordable system, the electricaleffects of the biobits is isolated from the tracking requirements of thesystem. The CD recordable wobble signal is generated in the radial planeand cannot be detected in the HF servo signal. The radial plane isprimarily detectable in the tracking signal. Very little informationfrom radial components are detectable in the HF signal. This allows usto isolate the tracking signal from the HF or Quad sum signal. Thissignal isolation is advantageous to the application of detectingbiobits.

[0274] The effect of biobits on the wobble signal can be described bythe following mathematical relationships. On the current CD-recordablesystem a wobble signal is utilized at a locking frequency of 22.05 kHzor 45.35 msecs. At a linear velocity of 1.2 meters/sec we would comparea single wave of the wobble pattern to a physical component of 54.42microns. In other words, we are able to detect physical features in theradial plane that are very large.

[0275] By using this isolation technique we will be able to detect verylarge features without losing tracking. The successful physicalmeasurement of a biobit can be determined by monitoring the HF andtracking signals simultaneously. If the biobit is small enough anelectrical deflection will be noted at the output of the Quad sum or HFsignal with no associated electrical impulse noted at the output of thetracking signal. There will, of course be some electrical impulse notedon the tracking signal but it will be very small in comparison. Asimilar relationship between the HF signal and the Focusing servo signalwill be noted.

[0276] With reference now to FIG. 12, there is shown an expanded view ofimplementation 11 (FIG. 9A) showing the optical disc assembly 130 withbio-bits, signal elements, or investigational features 136 inconjunction with optical disc drive 140, buffer amplifier card 152, ADC150, PC 158, and display 146 implemented according to the presentinvention. In one embodiment, raw detected signals (A, B, C, D, E, andF) are tapped off and fed directly into external buffer amplifier card152. In another embodiment, detected signals A, B, C, D, E, and F areprocessed in the optical disc drive's drive buffer 151 prior to enteringexternal buffer amplifier card 152. In yet another embodiment, bothtapped off raw signals and signals processed by drive buffer 151 are fedinto external buffer amplifier card 152. Signals exiting external bufferamplifier card 152 enter ADC 150 for further processing according toimplementation 11 (FIG. 9A) of the invention.

[0277] With continuing reference to FIG. 12, a drive motor 95 and acontroller 96 are provided for controlling the rotation of disc 130. Ahardware trigger sensor 141 may be used. Trigger sensor 141 provides asignal to ADC 150 that allows for the collection of data only whenincident beam 137 is on a target zone 135. Optical bio-disc 130 includesa trigger mark 166 that is read by trigger sensor 141, which feeds thetrigger signal to capture trigger card 167. Capture trigger card 167 ispreferably, but not necessarily, implemented on buffer card 152. Triggersensor 141 may be located on the bottom side of disc assembly 130. Thesystem may also include a top detector 160 for detecting transmittedlight 162. This light could pass through a semi-reflective disc, orthrough an area where portions of the reflective layer of the disc havebeen removed. Further aspects of the types of discs suitable for usewith the present invention are discussed below in further detail.

[0278]FIG. 13 shows a plan view of disc 130 with target zones 135 andtrigger marks 166. Hardware trigger mark 166 is preferably disposed atan outer periphery of the disc, and preferably is in a radial line withtarget zones 135.

[0279] Capture trigger card 167 provides a signal indicating whentrigger mark 166 has reached a predetermined position with respect toinvestigational features 136. This signal is processed through ADC 150,and into PC 158 to synchronize processing that takes place in PC 158with the location of trigger mark 166. For example, trigger mark 166 isplaced just prior to a sector in bio-disc 130 containing investigationalstructures. When PC 158 detects trigger mark 166, PC 158 waits a shortpredetermined time, and then begins processing the signal extracted fromthe HF signal as data indicative of the presence of an investigationalfeature. At the same time, when trigger mark 166 is detected by PC 158,PC 158 sets a timer for a longer predetermined time after which PC 158again processes the signal extracted from the HF signal as operationinformation used to operate the optical disc drive.

[0280]FIG. 14 is a block diagram showing the relationship of PC 158 withoptical disc drive 140. According to an embodiment of implementation II(FIG. 9A) of the present invention, additional drive functionality,including top detector 160, trigger sensor 141, and processingcircuitry, is preferably located on a single printed circuit board (TAD)82. This functionality thus detects transmitted light and trigger marks,and then amplifies an analog data signal based on the detectedtransmitted light. These additions are preferably made so that no changeis needed to existing optical disc drive electronics. Therefore, aconventional optical disc drive may be modified prior to initialshipment, or retrofitted with the additional functionality without theneed to alter existing hardware.

[0281] According to another embodiment of the invention, and as analternative to trigger mark 166, the trigger signal 83 could be providedin the operational data, such that encoded information on the discindicates the location of the investigational features. In yet anotherembodiment, the entire disc is read, but only the data following apredefined set of data is maintained. In this way, all of the data onthe disc is initially read into memory, and the data preceding thesoftware trigger is later discarded. Optionally, a second trigger markcan be provided. This second mark can be useful to distinguish fromamong multiple target zones, while enabling the user to look at aparticular zone of interest. If multiple trigger marks, withcorresponding trigger detectors, are used, then each trigger mark mustbe located at a different radius.

[0282] ADC 150 may also receive analog drive signals via bufferamplifier card 152, which receives its input signals from optical drive140. Within PC 158, CPU motherboard 87 communicates with optical discdrive 140 over a small computer systems interface (SCSI) 88 and receivesdata through an expansion bus from ADC 150. CPU motherboard 87 has anEthernet connection 88 that allows this data to be offloaded for furtherprocessing. A power supply 89 receives a power input and provides thepower to CPU motherboard 87 as well as to the other components in theoptical disc drive housing and in PC 158.

[0283] The data can be processed as it is collected in a real-timemanner, or may be stored and post processed by other computers,potentially reducing the complexity of the system.

[0284] The trigger, amplifier, detector card TAD 82 is preferablyconstructed in such a manner that it can be mounted within aconventional optical disc drive of the type that can be used in a drivebay in a computer. One suitable drive used particularly for developmentpurposes is the Plextor model 8220 CD-R drive. While a CD or DVD can beused, a CD-R drive has several useful aspects. Because the CD-R driveallows reading and writing functions, the laser can operate over ahigher range of power levels. This functionality of using higher powercan be useful for certain types of investigational features. Anotheruseful aspect of a CD-R is that it has the ability to write onto a discand therefore can be used to write results back onto a disc. This allowsresults to be saved back onto the disc for later use and to remain withthe disc.

[0285]FIG. 15 is a top view of TAD 82 including a triggering detectionassembly according to another aspect of the present invention. Thecircuit board includes an opening or pass-through port 80 which isneeded when implemented in a top detector drive arrangement utilizing atransmissive disc such as those disclosed in commonly assigned U.S. Pat.No. 5,892,577 entitled “Apparatus and Method for Carrying Out Analysisof Samples,” incorporated herein by reference, and U.S. ProvisionalApplication No. 60/247,465 entitled “Disc Drive for Optical Bio-Disc.”When employed with conventional drives using reflective discs and atypically positioned proximal or bottom detector, the pass-through port80 is not required. As discussed in conjunction with FIG. 12, the TAD 82includes trigger sensor 141 and the detector 160. In this particularembodiment, three detectors 160 are used.

[0286]FIG. 16 is an electrical schematic of the triggering circuit shownin FIG. 15. To acquire information concerning the investigationalstructures, the optical disc drive according to the present embodimentis provided with suitable triggering circuitry implemented to triggerwhen detection of the unprocessed HF signal 50 (FIG. 4) is needed. Thisis necessary because the type of signal processing performed by DSP 32(FIG. 8), which typically includes demodulation, decoding, and errorchecking, is intended to convert EFM-encoded information on HF signal 50to a specific digital format. Although the portion of the disc thatprovides operational information produces digital formatted data, theinvestigational features of the present invention do not produceEFM-encoded information. HF signals processed in a manner to decodeEFM-encoded information cannot be easily used to detect the dual peaksassociated with investigational structures. Thus, the signal or signalsof interest are tapped-off before reaching the optical drive's DSP, andtrigger mark 166 and trigger circuitry shown in FIGS. 14 and 26 areimplemented as discussed above.

[0287]FIG. 17 is a block diagram that illustrates in more detail theinter-relationship between TAD 82 and the disc drive mechanisms. As itis shown here, optical components 92 are mounted on a carriage assembly172 that is driven by a carriage motor 94, and the disc is driven by thedisc motor 95. The carriage assembly 172 includes an optical pick-upunit (OPU). Controllers 96, which receive signals from CPU 87, drive thetwo motors. Data from the optical components 92, triggering detectorsignal 83, and signals 83 from transmissive (top) detector 160 ordetector array are all provided to TAD 82. The detector for processingthe signal from the transmitted or reflected beam of light may be asingle detector element or an array of multiple elements arrangedradially or circumferentially, and may be placed on the opposite side ofthe disc from the laser, and may be mounted directly on the TAD orseparately.

[0288] ADC 150 may optionally be located on a sampling card that allowsfor very high-speed conversion. One usable card is the Ultrad AD 1280DX, which has two 12-bit A/D converters sampling up to forty millionsamples per second.

[0289] There are advantages to making changes to the disc drive thatprovide the least amount of disruption to conventional drives. For thisreason, it can be desirable to use a disc that is transmissive. In otherwords, the disc is reflective enough for the operational data to be seenby the active electronics and normal drive functioning to occur. Yet,still partially transmissive to allow some of the incident light to passthrough the disc to a top detector. In this manner, the investigationalfeatures can be detected without it being necessary to alter thedetection circuitry for reflected light. The reflected light may stillbe used to read encoded data.

[0290] Referring next to FIG. 18, TAD 82 illustrated by functionalblocks can include transmissive or top detectors 160 located over theviewing regions or pass through port 80 as illustrated. This detectorcan be a single detector, an array arranged with different segmentsoriented radially, or an array with multiple segments orientedcircumferentially with multiple detectors arranged along differentradii. The detector unit 160 receives signals and provides them to apreamplifier 120, automatic gain control 122, switch 124, and amplifier126 to produce a signal on the order of 3 volts.

[0291] Triggering light source and detector 141 can be provided on TAD82. This hardware would include a light source and a detector positionedto detect trigger marks, preferably at the periphery of disc 130. Inthis particular embodiment, a second trigger light source and detector128 is provided to help distinguish from among a plurality of triggermarks. In this case, both trigger signals are provided to a triggercontrol circuit. The trigger control circuit passes trigger signals tocollect and retain data from the desired sample areas on to ADC 150.

[0292] Analog switch 124 can be used when the data detector is an arraywith multiple elements. There can be multiple detector elements thatperform some of the types of refracted light combinations. For example,sums and differences can be used. If desirable, the switch can also becoupled to the detection elements that are under the disc for detectingreflected light. This could allow the system to obtain a differentialbetween the top and bottom detection.

[0293] Additional processing and counting functionality can be providedon TAD 82 in order to remove the processing from ADC 150, or toeffectively replace ADC 150 and PC 158 (FIG. 9A) to allow moreprocessing to occur on TAD 82. In the case of the test for CD4/CD8, forexample, one methodology that is used is to count white blood cells in atarget region. Such methods are disclosed in commonly assigned U.S.patent application Ser. No. 09/988,728 entitled “Methods and Apparatusfor Detecting and Quantifying Lymphocytes with Optical Biodiscs” filedNov. 16, 2001. As the laser light is scanned over the assay region, thedetector will detect no light at the edge of a blood cell, and willdetect full light when centered on a blood cell. As the beam is scanned,it therefore creates a series of high and low signals indicating where acell is detected. Processing functionality can be added to the card toinclude threshold crossing circuitry and a counter. Such processing isless complex than that which may be used for other tests. Each of thesetypes of circuits is generally known. Depending on the type of test thatis used (the CD4/CD8 being one example), the processing system may needto count hundreds or up to tens of thousands of features in the assayregion or target zone. In addition, a microprocessor could also be addedto the card.

[0294] By providing additional processing and/or counting functionalityonto the card, the results from scanning the sample can be provideddirectly from the card via a USB port or through an Ethernet port. Byusing Ethernet, data can be provided from a web server so that users canaccess data with a web browser.

[0295] TAD 82 can also include a temperature sensor (not shown) as wellas other sensors that may be useful for testing. In the case oftemperature, a test may use relative temperature to indicate thepresence of some material. Another detector that can be provided is asimple barcode reader that can be used if barcodes are provided on thedisc for identification purposes.

[0296] The automatic gain control (AGC) 122 and automatic level control(not shown) make sure that the full dynamic range is used, and thus thesignals may range, for example, from 0 to 3 volts. The automatic levelcontrol (ALC) is used to define a center of the signal, such as 1.5volts if, for example, the range is 0 to 3 volts. The result of theamplification, ACG, and ALC is that the output can be processed througha threshold circuit and provide consistent results.

[0297] As a concrete example of the embodiments depicted in FIGS. 9A and12, an inventive drive of the present invention includes a known opticaldisc drive that has been modified to include capture trigger card 164,buffer 152 and ADC 150. The inventive drive and a setup optical disc aresold, for example, to a research laboratory. The setup optical disccontains drive software and is of a known type of optical disc. Theresearch laboratory connects the inventive drive to a known PC (e.g., PC158) and runs the setup optical disc to install drive control softwarethat enables PC 158 and the inventive drive to operate as a researchinstrument. Then, diverse types of optical bio-discs 130, that includetrigger mark 166 and target zones 135, are sold to the researchlaboratory to enable diverse investigations and assays to be conducted.Bio-disc 130 may include target zones 135 and related microfluidics inone sector and encoded information in another. The encoded informationincludes operational information used to operate the optical disc driveand includes data about the type of tests that may be performed by theparticular optical analysis disc. Different tests may require differentdiscs and the encoded information on the disc then provides PC 158 withinformation about the particular test being run.

[0298]FIG. 19 is a top plan view of an optical disc drive assembly withthe housing removed to show the disc tray 168, the spindle 170, thecarriage assembly 172, the optical head assembly 174, and the ribboncable 178, which transmits signals to and from the optical headassembly. The carriage assembly 172 provides linear movement to opticalhead assembly 174 along rails 173. Optical head assembly 174 containslens assembly 176 for focal adjustments of incident and reflected light.

[0299]FIG. 20 is a bottom perspective view of the optical disc driveassembly of FIG. 19, illustrating the physical layout of the chip set,related electronic circuitry, and ribbon cable 178 from head assembly174 (FIG. 19) as unplugged from ribbon cable connector 179 on circuitboard 177. Signals transmitted to and from optical head assembly 174 maybe acquired either directly from ribbon cable 178, at the leadsconnecting ribbon cable connector 179 to circuit board 177, or atparticular solder points 180 on circuit board 177.

[0300]FIG. 21 is a block diagram depicting interconnections betweenprior art optical disc reader 140 and buffer amplifier card 152according to an embodiment of implementation 11 (FIG. 9A) of thisinvention. A chip set 30 (FIG. 8) according to the present invention isshown to include taps from the A, B, C, and D outputs of detector 18.FIG. 21 further illustrates that the F−, F+, T−, T+, HF-AC coupled, andHF-DC coupled signals may also be tapped off of the HF matrix amplifier18A of optical disc drive 140. These tapped signals provide access toraw, unprocessed analog signals produced by detector 18 and by the HFmatrix amplifier 18A. This permits external instrumentation to receivethe signals without interfering with normal drive operation. Suchexternal instrumentation may alternatively include the modified PC 142,the audio processing module 156, the external ADC 150, or the externalbuffer amplifier card 152 and external ADC 150 as shown in FIG. 9A. Asindicated above, FIG. 21 is directed to implementation 11 of theinvention as generally illustrated in FIG. 9A.

[0301]FIG. 22 is a top perspective view of one physical embodiment ofthe external buffer amplifier card 152 (FIGS. 9A and 21) adapted toreceive signals from optical head assembly 174 (FIG. 19) and drivebuffer 151 (FIG. 12) according to the A to D embodiment of the presentinvention. This electrical device outputs and buffers the operationalsignals of an optical disc drive. Signals from optical head assembly 174enter buffer amplifier card 152 at the pins of connector 155. Thesignals are amplified and buffered via independent groups of resistors,capacitors, and op amps, then directed to output section 157. Thisembodiment of buffer amplifier card 152 provides 9 to 11 output signals,including Quadrant A, Quadrant B, Quadrant C, Quadrant D, Detector E,Detector F, Un-Equalized HF, Equalized HF, AC coupled HF, Tracking servoresponse, and Focus servo response.

[0302]FIG. 23 is a perspective view of an alternative embodiment ofexternal buffer amplifier card 152 illustrated in FIG. 22. The inputsignals from the optical head assembly enter at connector 155. Thesignals directed to the optical disc drive's internal drive buffer 151(FIG. 12) exit through output section 157, while processed signals aredirected through connector 159 to external buffer amplifier card 152(FIG. 12).

[0303]FIG. 24 is a graphical representation illustrating therelationship between FIGS. 24A, 24B, and 24C. FIGS. 24A, 24B and 24C areelectrical schematics of the amplifier stages according to a firstembodiment of the buffer cards shown in FIGS. 22 and 23.

[0304]FIG. 24A is a partial electrical schematic of the bufferamplifier. The analog HF signal 50 (FIG. 4) from optical head assembly174 (FIG. 19) is taken from pins 1 and 2 of connector 155 (FIGS. 22 and23). The input signal travels across an input load resistor and avoltage stabilization capacitor to equalize background noise between thepositive and negative leads. The positive signal is then fed into an opamp, which is buffered with a variable feedback loop. The amplifiedsignal is directed across an output load resistor and stabilizationcapacitor before becoming the HF1 signal output at connector J5 ofoutput section 157 (FIG. 22).

[0305] The analog F+ signal from optical head assembly 174 is taken frompins 3 and 4 of connector 155. The input signal travels across an inputload resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the FC+ signal.

[0306] The analog F− signal from optical head assembly 174 is taken frompins 5 and 6 of connector 155. The input signal travels across an inputload resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the FC− signal.

[0307] The analog T+ signal from optical head assembly 174 is taken frompins 7 and 8 of connector 155. The input signal travels across an inputload resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the TC+ signal.

[0308] The analog T− signal from optical head assembly 174 is taken frompins 9 and 10 of connector 155. The input signal travels across an inputload resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the TC− signal.

[0309]FIG. 24B is another partial electrical schematic of the bufferamplifier. The analog HF-AC signal from optical head assembly 174 (FIG.19) is taken from pins 11 and 12 of connector 155 (FIGS. 22 and 23). Theinput signal travels through an input load capacitor, then across aninput load resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a variablefeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the HF-AC signaloutput at connector J3 of output section 157 (FIG. 22).

[0310] The analog HF-A signal from optical head assembly 174 is takenfrom pins 19 and 14 of connector 155. The input signal travels across aninput load resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the HF-A signaloutput at connector J8 of output section 157. The signal is also tappedat the output lead prior to the stabilization capacitor to feed an HF-Asignal into the A to D circuit of the HF2(DC) output at connector J7(FIG. 24C).

[0311] The analog HF-B signal from optical head assembly 174 is takenfrom pins 17 and 16 of connector 155. The input signal travels across aninput load resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the HF-B signaloutput at connector J9 of output section 157 (FIG. 22). The signal isalso tapped at the output lead prior to the stabilization capacitor tofeed an HF-B signal into the A to D circuit of the HF2(DC) output atconnector J7 (See FIG. 24C).

[0312] The analog HF-C signal from optical head assembly 174 is takenfrom pins 15 and 18 of connector 155. The input signal travels across aninput load resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the HF-C signaloutput at connector J10 of output section 157 (FIG. 22). The signal isalso tapped at the output lead prior to the stabilization capacitor tofeed an HF-C signal into the A to D circuit of the HF2(DC) output atconnector J7 (See FIG. 24C).

[0313] The analog HF-D signal from optical head assembly 174 is takenfrom pins 13 and 20 of connector 155. The input signal travels across aninput load resistor and a voltage stabilization capacitor to equalizebackground noise between the positive and negative leads. The positivesignal is then fed into an op amp, which is buffered with a fixedfeedback loop. The amplified signal is directed across an output loadresistor and stabilization capacitor before becoming the HF-D signaloutput at connector J11 of output section 157 (FIG. 22). The signal isalso tapped at the output lead prior to the stabilization capacitor tofeed an HF-D signal into the A to D circuit of the HF2(DC) output atconnector J7 (See FIG. 24C).

[0314]FIG. 24C is yet another partial electrical schematic of the bufferamplifier. The FC+ and FC− signals from FIG. 24A are directed throughindependent input resistors and then combined. The combined signal isfed into the negative input of an op amp, with a variable positivevoltage feeding the positive input. The amplified signal is bufferedwith a fixed feedback loop and directed through a variable resistor intothe negative input of a second op amp. The amplified signal from thesecond op amp is buffered with a second fixed feedback loop and directedacross an output resistor and stabilization capacitor before becomingthe FOCUS output at connector J2 of output section 157 (FIG. 22).

[0315] The TC+ and TC− signals from FIG. 24A are directed throughindependent input resistors and then combined. The combined signal isfed into the negative input of an op amp, with a variable positivevoltage feeding the positive input. The amplified signal is bufferedwith a fixed feedback loop and directed through a variable resistor intothe negative input of a second op amp. The amplified signal from thesecond op amp is buffered with a second fixed feedback loop and directedacross an output resistor and stabilization capacitor before becomingthe TRACKING output at connector J6 of output section 157 (FIG. 22).

[0316] The tapped HF-A, HF-B, HF-C, and HF-D signals from FIG. 24B areindividually directed through input resistors and then combined asillustrated. The combined signal is fed into the negative input of an opamp, with a variable positive voltage feeding the positive input. Theamplified signal is buffered with a fixed feedback loop and directedthrough a variable resistor into the negative input of a second op amp.The amplified signal from the second op amp is buffered with a secondfixed feedback loop and directed across an output resistor andstabilization capacitor before becoming the HF2(DC) output at connectorJ7 of output section 157 (FIG. 22).

[0317] Modifying an Optical Disc Drive—Software

[0318] In accordance with other principles of the present invention, itis possible to programmably reconfigure chip set 30 (FIG. 8) so thatphysical modification of the optical disc drive is not necessary. Oneway this may be accomplished is by programming DSP 32 (FIG.8) to operatesimply as an A/D converter rather than as, inter alia, ademodulator/decoder. In such a configuration, the DSP chip takes theplace of external ADC 150 and supplies the digitized HF signals directlyto a host data bus. Investigational structures may be detected byanalyzing the resulting digitized HF signal. Alternatively,investigational structures could be detected by routing an unprocessedHF signal through the chip set 30 to an output terminal of optical discdrive 140 (FIG. 9A), connecting the signal to a personal computer (e.g.,PC 158), and using hardware and/or software within the personal computerto perform the A/D conversion.

[0319] It is possible to programmably configure DSP 32 as an A/Dconverter without additional demodulation and error correction inmultiple ways. For example, a configuration routine stored in programmemory 39 (FIG. 8) may operate via controller 38 (FIG. 8) to reconfigureDSP 32. Alternatively, an application program may be able to selectivelyreconfigure DSP 32 through interface circuitry 36 (FIG. 8) as required.DSP 32 may also configure itself as an A/D converter when it receives acertain type of HF signal. These methods are merely illustrative, andany other suitable software or firmware based reconfiguration methods orpath may be used if desired.

[0320]FIG. 25 is a functional block diagram of a digital signalprocessing circuit programmably configured as an analog-to-digitalconverter in accordance with the principles of an embodiment ofimplementation III the present invention as represented in FIG. 9A. FIG.25 illustrates some of the ways in which the processing resources withinDSP 32 may be reconfigured to produce a suitable A/D converter accordingto the present invention. In one possible arrangement, for example, A/Dblock 42 may be disconnected from path 45 and connected directly tooutput interface 48 through path 43. In this case, the digitized HFsignals completely bypass blocks 44 and 46 and travel to outputinterface 48. In another arrangement, digitized signals from A/D block42 travel on path 45, but pass through blocks 44 and 46 without beingprocessed. In some embodiments, it may be desirable to temporarilydiscontinue power supply to blocks 44 and 46 or place them in alow-power operating mode to reduce power consumption (e.g., in batteryoperated disc drives). Although the foregoing illustrates severalpossible A/D converter arrangements, any other suitable arrangement ofresources within DSP 32 may be used if desired.

[0321] If the bypassing of unneeded functionality can be accomplishedthrough programming, no change to existing hardware is needed, althougha modification may be needed to drive firmware.

[0322]FIG. 26 is a flow chart illustrating some of the steps involved indetecting investigational elements in accordance with the DSP embodimentof the present invention illustrated in FIG. 25. As shown in FIG. 26,when it is desired to enter detection mode (step 100), a portion of asignal processing system within the drive is configured to operate as ananalog-to-digital converter (step 101). This may include programmablyreconfiguring one or more chips in chip set 30 (e.g., DSP 32) byemploying a remote application program or by using a routine stored in alocal program memory 39, FIG. 6. This conversion eliminates the need tophysically modify the disc drive electronics, and it allows theinvention to take advantage of the configurable processing resourceswithin chip set 30.

[0323] At step 102, a plurality of analog data signals are acquired fromdisc 130 (FIG. 12), which preferably includes investigational structures136 (FIG. 12), using objective assembly 10 (FIG. 1). Next, at step 103the analog data signals are combined to produce a sum (HF) signal 50(FIG. 4) and a tracking error (TE) signal 52 (FIG. 4). Both signals areprovided to the signal processing system at step 104. At step 105, thebasic information required to operate the disc drive (such as tracking,focus, and speed control) is extracted from TE signal 52.Simultaneously, the signal processing system converts the HF signal 50into a digitized signal, which is provided to output interface 36 (FIG.8) at step 105. The digitized sum signal is subsequently used tocharacterize the investigational features or structures 136 present ondisc 130. Once the scanning process is complete, disc drive 140 may bedirected to exit the detection mode (step 106). At this point, theportion of chip set 30 (e.g., DSP 32) previously configured as an A/Dconverter may be returned to its original configuration and normal CD,CD-R, or DVD operation may resume (step 107).

[0324] In a variant of the trigger mark 166 (FIG. 13) and triggercircuit 167 arrangement, a registration mark on optical disc assembly130 itself may be encoded and recorded. Certain digital binaryautocorrelation codes (i.e., a sequence of binary bits) may be used toencode the registration mark. For example, the known Barker code is aseries of bits (varying in number up to thirteen bits) that has a sharpautocorrelation function with a peak equal to the number of bits (whenregistered or correlated) and side lobes (when not registered orcorrelated) equal to one. See Barker, R. H., “Group Synchronization ofBinary Digital Systems,” as it appears in Jackson, W. (ed.),Communications Theory, Academic Press, New York, 1953, pp. 273-287,incorporated herein by reference.

[0325] In a concrete example, one thirteen bit Barker code is known tobe 1111100110101. When a digital bit stream containing this 13 bit longcode is correlated with a receiver searching for this 13 bit long codeas a reference, a perfect registration will produce a correlation with13 identical bits. However, if the bit stream were to be slid forward orback by up to 12 bits, the peak correlation side lobe would be only 1bit.

[0326] Other autocorrelation functions are known with low side lobe outof correlation values and high in correlation values. See Lindner, J.,“Binary Sequences Up To Length 40 With Best Possible AutocorrelationFunction,” Electron. Letters, vol. 11, p. 507, October 1975. Forexample, there are two known codes of length 25 bits, one of which,expressed in octal, is 163402511. An octal digit varies from 0 to 7 andrepresents, in order, binary 000, 001, 010, 011, 100, 101, 110, and 111.This code has a maximum peak side lobe of 2 and a correlation peak of25. There are 114 known codes of length 40, one of which, expressed inoctal, is 14727057244044. This code has a maximum peak side lobe of 3and a correlation peak of 40.

[0327] Long autocorrelation codes are also characterized by lowcorrelation values with random bits received in a sequence, and highcorrelation values when the exact code is detected and registered in thebit stream. A bit stream recorded on an optical disc assembly might beconstructed to include an autocorrelation code within the data bitstream. A signal processor that analyzes the bit stream would thencorrelate the bit stream with the autocorrelation code being soughtwithin the incoming bit stream. When the correlation processorencounters the autocorrelation code in the bit stream, the correlationfunction spikes up very high in relation to normal correlation valueswith random bit stream data. This provides a registration mark in thesame sense that trigger mark 166 provides a registration mark.

[0328] Referring again to FIG. 12, optical disc assembly 130 is dividedinto a sector with investigational features or signal elements 136situated within target zones 135 and a sector 133 containing operationalinformation used to operate the optical disc system. In this variant,the operational information advantageously includes data, at least someof which includes an autocorrelation code. This data is stored on asector of optical disc assembly 130 in known ways (e.g., CD ROM, DVD,etc.). When the autocorrelation code is detected and registered in thedata stream from the optical disc assembly, two timers are set in PC 158(or equivalent circuitry). The beginning of the sector containing theinvestigational features is marked by an expiration of the first timer,and the ending of the sector containing the investigational features ismarked by an expiration of the second timer. The duration of the twotimers is advantageously included in the data stored on optical discassembly 130 so that a common disc drive system can be used fordifferent types of bio-discs with different size sectors in which theinvestigational features are stored.

[0329] A conventional optical disc reader generally allows a user toplay a disc, while giving the user little ability to control theparameters of the reading, rotating, and data processing. For the mostpart, users of commercial CD and DVD players would not need suchabilities. These firmware-based modifications can generally be madeusing aftermarket software. In other words, the programming could beprovided on a disc or could be available by download via the Internet.

[0330] Another modification to the conventional CD reader is a techniqueshown on FIG. 87. Channel bit generator 1000 is used to generate knowngood data bits and then add them to the data bits actually received fromthe read out of an optical disc containing bio-bits, as represented bypick up 1002. The sum of bits is then sent to block decoder 1004 whereblock error information can be obtained.

[0331] Additional modifications suitable for use in the inventioninclude, but are not limited to, one or more of the followingcapabilities:

[0332] 1. Wobble groove playback and random access on a wobble groove,rather than needing to start from the beginning of a disc. This allowsthe drive to go to an LBA (or an address by some other mode) and playforward from there.

[0333] 2. Poll the laser monitor value, which allows reading of thevalue of the laser power detected by the laser power monitor detector inthe optical pickup unit.

[0334] 3. Poll and set the laser power read/play value, which allows auser to monitor and set the power command value to the laser.

[0335] 4. Poll the automatic gain control (AGC) to get the value of theAGC. The gain is controlled to make sure that the detected signals haveconsistent amplitude. The amount of gain therefore is an inverseindicator of the signal intensity. Consequently, the signal can be usedfor detection and measurement.

[0336] 5. Poll the tracking automatic gain control value.

[0337] 6. Monitor the C1 and/or P1 decoder activity at a port to monitortypes of errors and attain error counts. This is useful because theerrors could be useful information for detecting the location of aninvestigational feature. A conventional drive detects gaps in theencoded data as an error.

[0338] 7. Monitor the C2 and/or PO decoder activity at a port. See No. 6above.

[0339] 8. Initialize and track operational features on an analysis discindependent of encoded logic. This refers to the ability to control thelaser position and control the speed of the disc independent of thedata. This functionality allows a user to send a command to keep thedrive motor spinning without its operational functions of focus,tracking, and synchronization.

[0340] 9. Initialize the drive with a specific speed and laser readpower. A drive typically has a fixed start-up speed and laser power.This change allows these values to be set and changed by the user. In atypical disc drive system, however, the disc immediately starts to spinto get a focal, point, get synchronization information, and find a tableof contents. If the information is not found, the disc drive will openup and shut down. In certain circumstances, it may be desirable not tospin the disc as soon as it is inserted into the disc drive. Forexample, it may be desirable to prevent the drive from automaticallyspinning when a liquid sample is added to the disc. This change alsorelates to the change set out in No. 15 below.

[0341] 10. Stream the main and sub-channel data in all areas of the discincluding lead-in and lead-out, which allows more portions of the discto have data.

[0342] 11. Push raw-EFM (eight-fourteen modulation) value to a port orsecondary port, which allows the user to see 14-bit data before it istranslated to 8-bit values. This functionality enables the user to moreclearly know exactly what is on the disc. Like No. 10 above, this changeallows additional areas on the disc to be used.

[0343] 12. Push buffered, DC coupled signals, such as TE, FE, and HF, toan external port. This relates to the ability to provide these signalsto an external port for additional processing, whereas they aregenerally used for internal purposes (see FIGS. 4 and 8).

[0344] 13. Decode and poll values collected from the power calibrationarea (PCA) and program memory area (PMA) at initialization. This allowsadditional information to be collected.

[0345] 14. Pause playback of a disc and open the tracking servo tomonitor the open loop tracking signal, which allows the user to monitorthe eccentricity of the disc. A disc generally has some eccentricity andtherefore, the tracking signal will have a periodic form as the disc isrotated. The eccentricity of the disc arises from imperfect processingof the disc. The tracking signal is thus a reflection of theeccentricity that produces a periodic signal, which is a reflection ofthe eccentricity. If there is a change in reflectivity in one area, suchas due to the presence of an investigational feature, the trackingsignal will reflect this change in reflectivity.

[0346] 15. Set Ghost initialization logic. As indicated in No. 9 above,when a disc is put into a disc drive, it typically starts spinning. Oneof the initial functions is to find a table of contents. Accordingly,this change allows the user to provide a table of contents to the discdrive controller effectively tricking the disc drive into thinking thatit has read the table of contents from the disc.

[0347] 16. Interactively turn off tracking function.

[0348] 17. Control and monitor the focusing offset with or without thetracking function. The focus offset changes the size of the laser spot,and thereby changes the amount of energy incident upon the disc. Incertain circumstances, it may be desirable to provide heat to the discor a region of the disc for optimal assay conditions. Therefore, theability to control the focus offset can allow the user to control heatdistribution.

[0349] 18. Switch layers on a DVD.

[0350] 19. Monitor value changes at the switching port.

[0351] 20. Read a CD or CD-RW with a DVD laser. The DVD laser is at alower wavelength, which can be useful for imaging and for fluorescentdetection. Devices that have the ability to read CD and DVD aregenerally provided with two lasers, one for each mode.

[0352] 21. Track a wobble groove (1.2 mm) at any frequency with a DVDlaser.

[0353] 22. Monitor the value of a buffered differential phase detection(DPD) signal. The DPD signal is a DVD signal used for tracking, and thuscorresponds to the previously discussed ability to monitor the trackingsignal.

[0354] 23. The use of a near field optical assembly to detect structuresthat violate the diffraction limitations of the laser diode.

[0355] 24. Utilize the servo to detect defect or structure. Servo willpush signal one way when the defect or structure is about the surface.The servo will go another way when the defect or structure is below thesurface.

[0356] 25. The use of phase delay detection in a DPD optical assembly todetect the presence of structures on an optical disc.

[0357] 26. The use of DPD focus servo electronics to detect the presenceof structures that generate digital biology components.

[0358] 27. Creation of a second surface mastering system that utilizedwobble tracking. A DVD RAM drive is used as a base unit and a DVD masteris created using wobble groove tracking. The pits are formed fromAblation.

[0359] 28. The use of a secondary focus place and a second laser toisolate the tracking system from the biobit detection plane and system.This design will be effected by the characteristics of the distributionof the biobit spheres.

[0360] Using EEPROM to Upgrade Existing Optical Drive

[0361] Some of the software modification described in the previoussection can be made via a software upgrade to the Electrically ErasableProgramming Read Only Memory (EEPROM) in existing optical drive. Whenutilizing a consumer optical disc reader it is possible to upgrade orconfigure the operation of the reader by uploading a program to anEEPROM in the optical disc circuitry. The program will replace or appendthe information that is in position on the EEPROM. The program iswritten to optimize the operation of the drive for the measurement ofbiological substance or biobits. The program will also change theaspects of the information that is used to communicate with the drive.The program will also change the information that is collected from thedrive during or after measurement or detection operation.

[0362] The program may be contained on the optical disc in a bootable(EL Torito Specification) format. A byte is placed in a known positionor sector (CD or DVD sector) that tells a qualified operating system(bootable BIOS or firmware) to utilize the information on the disc as anOperating System. This capability is common to most BIOS or other I/Osystems in the market place (i.e. Adaptec, Award, Phoenix, etc.). Ineffect, the identified byte will tell the computing device to reload theoperating system that is contained on the disc. The operating systemwill then run a loading program that is contained on the disc.

[0363] The loading program is written to manufacturer specifications informat. The loading program is written to application specifications incontent. The loading program is moved into the EEPROM in the circuitryof the drive by using the communication protocol of the port. Theseprotocols include the byte commands outlined in the industryspecification for ATAPI 1 & 2 (Small Form Factor Committee 80201-80901)and SCSI device formats for SCSI 1, 2 and 3 (ISO Standards). Thephysical outline of communication for SCSI and ATAPI devices arephysically different. Some manufacturers are allowed to use aproprietary byte communication format that is not covered in thestandard. The present invention may utilize these proprietaryspecifications. The Chipsets that are utilized by the drivemanufacturers also have some protocols that will be documented in theprogram form and the program content.

[0364] The information that is gathered from the drive during operationis gathered from the drive through the port (SCSI or ATAPI) and isinterpreted by a software program called a driver. The driver may be aproprietary driver contained in part by the operating system (e.g.Microsoft Windows™) or in part by the manufacturer of the drive. Thedriver may also be contained in part by the manufacturer of the chipsetthat is used to operate the communication port electrically. The drivermay also be replaced or amended by a program that is applicationspecific and is loaded into the operating system by the loading programon the disc.

[0365] The data that is gathered from the adjusted drive is gatheredfrom the physical port and interpreted by the driver. The data that iscollected is also outlined in form by the Specifications forcommunication with ATAPI and SCSI devices. The data may also becollected through a proprietary format that is loaded on the drive. Thisproprietary format may include adjusted chipset communication protocol,adjusted port communication protocol or an adjusted or non-standarddriver.

[0366] The specific data area involves collection of data from theoperation of the Reed-Soloman decoder of the optical disc reader. Thisincludes the C1 and C2 activity of the CIRC (Cross Interleaved ReedSoloman) code of an optical disc playback unit, the inner and outerparity activity of the RSPC (Reed-Soloman Product) code of a DVDplayback unit, or the CCRC/CRC (Cyclic Redundancy Check Code)information from any block or sector structure contained in an opticaldisc format. The data is provided to the port or the driver in packetformat and is relevant to the biological measurements that the presentinvention is designed to make.

[0367] DVD Technology

[0368] The use of DVD technology provides a dramatic increase in theoperational margin that is offered by the lower wavelength in the laserdiode, and by the drastic increase in density and operationalinformation that is included in the disc format. The bio-bits or signalelements including beads, cells, colloidal gold, carbon, or othermicroscopic markers and reporters associated with an optical disc, canbe located on layer 0 or layer 1 of a DVD disc assembly. Disc designsrelating to this aspect of the present invention are more fullydescribed in commonly assigned co-pending U.S. patent application Ser.No. 10/006,620 entitled “Multiple Data Layer Optical Discs for DetectingAnalytes”, filed Dec. 10, 2001, which is herein incorporated byreference.

[0369] Layer 0 of a DVD disc is manufactured as a second surface disc.This disc can be manufactured with very little information at the innerdiameter so that it will not interfere optically with the detection ofbio-bits on the outer diameter of layer 1. Layer 0 may be utilized as anadaptable optical spacer that is placed on layer 1 after processing abio-bit application. Layer 1 is manufactured as a first surface layer.Normally, it is glued onto layer 0 with special glue that has similarrefractive properties to the molded plastic layers (e.g., between 1.54and 1.58). This maintains optical efficiency and very little loss ofsignal in the reflected or return path. The specified thickness of thislayer is 40-60 microns. The transmissive properties of the outer layer,or layer 0, are preferably then designed to make up for a significantloss of signal resulting from a tiny air interface.

[0370] The DVD system is designed to provide automatic signal gain andrecover information from surfaces with a reflectivity as low as 30%(only defined for dual layer formats). Automated tilt control may benecessary for this method. The use of multiple lasers will be utilizedin this technological application. Layer 0 may become an operationallayer that will contain information to provide for the operationalrequirements of the system. A second layer will be used on layer 1 thatwill detect the bio-bits, signal elements, or investigational features.Layer 1 may or may not contain pits, lands, or grooves. In oneparticular embodiment, the bio-bits, signal elements, or investigationalfeatures are applied to a DVD-R, DVD-RW, or DVD-RAM application withzoned clocking or pitted wobble groove applications. A “hybrid” disc ina DVD system is employed as a stepping-stone for this bio-bit detectiontechnique. The word “hybrid” entails the use of multiple densities. Forexample, layer 0 is of DVD density and layer 1 is of CD density.

[0371] The idea is to create a hybrid sick such as the one shown inFIGS. 88A and 88B. FIG. 88A is a side view of the hybrid disc and FIG.88B is a top view of the disc. An 8 cm CD is manufactured and adhered tothe center of a single laser DVD-RAM or DVD-RW disk. The CD portionwould basically represent later 1 of a DVD disk and include informationrelated to performing the bio assay, such as programs for the driveelectronics, disk speed, etc. As shown in FIG. 88A, layer 1 1008 (8 cmCD layer) is on top of layer 0 1006. Underneath layer 0 (1006) issubstrate layer 1016. At the end of a CD portion, the drive isinstructed to skip to layer 0 1006 and being reading the outer portionof the disk. The structures to be measured are located in the recess1014 on the underside of the cover 1012. Several recesses aredistributed across the different sectors of the disc, in the outerportion of layer 0 (1006), as shown in FIG. 88B. In an alternateembodiment, capillary tubes could be used instead of a recess. Since thespace between layers L0 and L1 is in the order of 40 um, there is roomfor potentially large biological structures.

[0372] With this embodiment, the cover contains the bio-assay and isreplaced for each assay performed. The remainder of the disk could bereused for further assays provided it could be cleaned to prevent crosscontamination.

[0373] One development in DVD technology enables a DVD drive totemporarily reprogram itself from information contained on a disk beingread. This would provide a means for reprograming DVD drive electronicsto perform any special processing required to detect the presence of thebio-bits, and to characterize any such bio-bits detected. For example,the bio-bits could be deposited in specific patterns on the disk. Thedisk would also include program code for detecting the presence ofabsence of the patterns and thereby detect the bio-bits. This wouldinvolve developing a code such as an RLL(2,10) code and programming theDVD electronics accordingly.

[0374] One difference in implementation in the DVD technology for thedetection of biobits involves the use of wobble signal. There aresignificant differences between the wobble signal utilized in the CDrecordable system and the DVD system. In the CD recordable system thepresent invention utilizes the wobble signal to provide a trackingsignal that can be compared to a reference pulse to maintain speedcontrol. The secondary wobble signal is very interesting. It utilizes abi-phase mark encoding technique and provides several other pieces ofinformation. The bi-phase mark method is a digital modulation method.This digital waveform is superimposed on the wobble signal and abi-phase decoder is included in the CD Recordable unit to decode theinformation. The digital information that is encoded in the wobblesignal includes logical position, power control information andspecialized use information. The manufacturing technique for bi-phasemark and wobble signal is very unique. Mastering a CD recordable masterrequires a very specialized mastering system. The mastering” system uses2 mastering lasers. One laser is utilized to make the wobbled groove anda secondary laser is modulated to create the bi-phase mark informationin the wobbled signal.

[0375] In the DVD recordable system, the components used that are verysimilar to the components described above. The technology on themastering level is somewhat similar in technique. The frequency(locking) utilized in this specification is 140 kHz or 7.143microseconds. At a rotational velocity of 3.49 meters/sec the physicalcomponent of one wobble pattern would equal approx. ˜25 microns. This isstill larger than most of the biological components that the presentinvention intends to measure.

[0376] Of greater concern is the design of the DVD rewritable standards.This standard utilizes a tracking and synchronization technique referredto as the wobbled land and groove format. The wobble signal frequency isincrease to 160 kHz or 6.25 microseconds. At a speed of 3.49 meters/sec,the physical component can be measured is about 21.8 microns.

[0377] In the DVD rewritable standard the address information that wasprovided by the bi-phase mark patterns in the CD Recordable standard isno longer digitally modulated on top of the wobble signal. Embossed pitstructures are placed at specific locations around the disc. These“Zones” contain the address information and some clocking information.This recording scheme is referred to as the ZCLV or Zoned ConstantLinear Velocity technique. The areas between these “zones” contain agroove and a wobble signal. A unique feature that is utilized in theDVD-RAM technique is the land/groove switch tracking. In this techniquewe switch from land on one rotation to groove on the next. This ishighly unusual but provides a high level of control. The lands haveembossed pit structures for control applications and the groove containsthe area for phase change recording.

[0378] In the present invention, the ability to decode the bi-phase markinformation is limited the biobit pattern density is increased. Thesezones provides the exact areas for the detection of biobit patterns.This technique uses space on the optical disc but the tradeoff is asignificant gain in the amount of positional accuracy.

[0379] Increasing Resolution

[0380] The power-monitoring signal in a CD or DVD recording systemprovides a response similar to that of a spectrophotometer. The powercontrol signal or monitor signal of a recording laser diode can becontrolled through logical information on the disc or through software.It may also include an analysis of the monitor signal as the focusedincident beam is moved across an area of the disc.

[0381] An alternative embodiment measures the birefringent properties ofan area on an optical disc. This would involve a modified player with asecond additional optical path that is currently not available in theconsumer market. This optical path involves the use of prisms instead ofa rotating polarimeter.

[0382] In the areas of mathematics that are used in the decodingprocessor of a player, the lookup table (that is used to performmodulation or the movement of information from the data bits to thechannel bits) can be replaced with a table to optimize detection ofbio-bits, signal elements, or investigational features. The mathematicsthat is adjusted to run length (RLL 2,10) in the Reed Soloman encodingand decoding scheme can be optimized for detection of bio-bits. Theseadjustments provide information that is used for detection orstatistical evaluation of bio-bits. The information is available usingstandard software detection of C1 or C2 errors on CD decoder interfaces.The information is also available utilizing standard software detectionof PI or PO errors on DVD decoder interfaces. The PI/PO data from theDVD decoder may be used to characterize the sizes of bio-bits, signalelements, and investigational features. In one particular embodiment,the EFM or ESM patterns generated by the lookup table are replaced withsimple 8-bit patterns that characterize the run length of the item understudy. Changes to the decoding system of a player may be performedthrough a program that is contained in the information stored on theoptical disc. The information is loaded into “Flash” EPROM or similartechnology.

[0383] Another alternative embodiment uses a Solid Immersion Lens (SIL)in the detection of bio-bit technology. A SIL player increasesoperational resolution significantly.

[0384] Yet another alternate embodiment uses a CD-Recordable player thatis optimized to read microscopic structures on the surface of an opticaldisc. The player is adjusted optically to detect the structures in theair interface on the surface of an optical disc. The disc is designed toutilize the CD-Recordable system to provide a platform for quantifiablemeasurement of microscopic structures.

[0385] Optical Bio-Discs

[0386]FIG. 27 is an exploded perspective view of the principlestructural elements of one embodiment of a particular optical bio-disc410. FIG. 27 is an example of a reflective zone optical bio-disc 410(hereinafter “reflective disc”) that may be used in the presentinvention. The principle structural elements include a cap portion 416,an adhesive member 418, and a substrate 420. Cap portion 416 includes aninlet port 422 and a vent port 424. Cap portion 416 may be formed frompolycarbonate and is preferably coated with a reflective surface 446(see FIG. 29) on the bottom thereof as viewed from the perspective ofFIG. 27. In the preferred embodiment, trigger marks 166 (FIG. 12) areincluded on the surface of the reflective layer 442 (see FIG. 29).Trigger marks 166 may include a clear window in all three layers of thebio-disc, an opaque area, or a reflective or semi-reflective areaencoded with information that sends data to a processor (e.g., ADC 150as shown in FIG. 12), that in turn interacts with the operativefunctions of the interrogation or incident beam 137 (FIG. 12). Thesecond element shown in FIG. 27 is adhesive or channel layer member 418having fluidic circuits 428 or U-channels formed therein. The fluidiccircuits 428 are formed by stamping or cutting the membrane to removeplastic film and form the shapes as indicated. Each of the fluidiccircuits 428 may include a flow channel 430 and a return channel 432.Some of the fluidic circuits 428 illustrated in FIG. 27 include a mixingchamber 434. Two different types of mixing chambers 434 are illustrated.The first is a symmetric mixing chamber 436 that is symmetrically formedrelative to the flow channel 430. The second is an off-set mixingchamber 438. The off-set mixing chamber 438 is formed to one side of theflow channel 430 as indicated. The third element illustrated in FIG. 27is substrate 420 including target or capture zones 135. Substrate 420 ispreferably made of polycarbonate and has a reflective layer 442deposited on the top thereof (see FIG. 29). Target zones 135 are formedby removing reflective layer 442 in the indicated shape or alternativelyin any desired shape. Alternatively, target zones 135 may be formed by amasking technique that includes masking the target zone 135 areas beforeapplying the reflective layer 442. Reflective layer 442 may be formedfrom a metal such as aluminum or gold.

[0387]FIG. 28 is a top plan view of the optical bio-disc 410 illustratedin FIG. 27 with the reflective layer 442 on the cap portion 416 shown astransparent to reveal the fluidic circuits 428, the target zones 135,the inlet ports 422, the vent ports 424, and trigger marks 166 situatedwithin the disc.

[0388] With reference next to FIG. 29, there is shown an enlargedperspective view of the reflective zone type optical bio-disc 410according to one embodiment of the present invention. This view includesa portion of the various layers thereof, cut away to illustrate apartial sectional view of each principle, layer, substrate, coating, ormembrane. FIG. 29 shows the substrate 420 that is coated with thereflective layer 442. An active layer 444 is applied over reflectivelayer 442. In a preferred embodiment, the active layer 444 may be formedfrom polystyrene. Alternatively, polycarbonate, gold, activated glass,modified glass, or modified polystyrene such as polystyrene-co-maleicanhydride, may be used. In addition hydrogels can be used.Alternatively, as illustrated in this embodiment, adhesive layer 418 isapplied over active layer 444. The exposed section of the adhesive layer418 illustrates the cut out or stamped U-shaped form that creates thefluidic circuits 428. The final principle structural layer in thisreflective zone embodiment of the present bio-disc is cap portion 416.Cap portion 416 includes the reflective surface 446 on the bottomthereof. Reflective surface 446 may be made from a metal such asaluminum or gold. Use of the type of disc illustrated in FIG. 29 withgenetic assays is disclosed in commonly assigned co-pending U.S. patentapplication Ser. No. 10/035,836 entitled “Surface Assembly forImmobilizing DNA Capture Probes and Bead-Based Assay Including OpticalBio-Discs and Methods Relating Thereto” filed Dec. 21, 2001, which isherein incorporated by reference.

[0389] Referring now to FIG. 30, there is shown an exploded perspectiveview of the principle structural elements of a transmissive type ofoptical bio-disc 410 according to the present invention. The principlestructural elements of the transmissive type of optical bio-disc 410similarly include cap portion 416, adhesive layer 418, and substrate420. Cap portion 416 includes inlet ports 422 and vent ports 424. Capportion 416 may be formed from a polycarbonate layer. Optional triggermarks 166 may be included on the surface of a thin semi-reflective layer443, as best illustrated in FIG. 33. Trigger marks 166 may include aclear window in all three layers of the bio-disc, an opaque area, or areflective or semi-reflective area encoded with information that sendsdata to a processor (e.g., ADC 150 as shown in FIG. 12), which in turninteracts with the operative functions of interrogation beam 137 (FIG.12).

[0390] The second element shown in FIG. 30 is an adhesive or channellayer member 418 having fluidic circuits 428 or U-channels formedtherein. The fluidic circuits 428 are formed by stamping or cutting themembrane to remove plastic film and form the shapes as indicated. Eachof the fluidic circuits 428 may include flow channel 430 and returnchannel 432. Some of fluidic circuits 428 illustrated in FIG. 30 includemixing chamber 434. Two different types of mixing chambers 434 areillustrated. The first is the symmetric mixing chamber 436 that issymmetrically formed relative to flow channel 430. The second is theoff-set mixing chamber 438. Off-set mixing chamber 438 is formed to oneside of flow channel 430 as indicated.

[0391] The third element illustrated in FIG. 30 is substrate 420, whichmay include target or capture zones 135. Substrate 420 is preferablymade of polycarbonate and has the thin semi-reflective layer 443 (shownin FIG. 34) deposited on the top thereof. Semi-reflective layer 443associated with substrate 420 of disc 410 illustrated in FIGS. 31 and 34is significantly thinner than the reflective layer 442 on substrate 420of the reflective disc 410 illustrated in FIGS. 27, 28 and 29. Thinnersemi-reflective layer 443 allows for some transmission of interrogationbeam 137 through the structural layers of the transmissive disc as shownin FIG. 12. Thin semi-reflective layer 443 may be formed from a metalsuch as aluminum or gold.

[0392]FIG. 31 is an enlarged perspective view of substrate 420 andsemi-reflective layer 443 of the transmissive embodiment of opticalbio-disc 410 illustrated in FIG. 30. In a preferred embodiment, thinsemi-reflective layer 443 of the transmissive disc illustrated in FIGS.30, 33, and 34 is approximately 100-300 Å thick and does not exceed 400Å. This thinner semi-reflective layer 443 allows a portion of incidentor interrogation beam 137 (FIG. 12) to penetrate and pass through thesemi-reflective layer 443 to be detected by a top detector 160 (FIG. 12)while some of the light is reflected or returned back along the incidentpath. As indicated below, Table 2 presents the reflective andtransmissive characteristics of a gold film relative to the thickness ofthe film. The gold film layer is fully reflective at a thickness greaterthan 880 Å. While the threshold density for transmission of lightthrough the gold film is approximately 400 Å. TABLE 2 Au film Reflectionand Transmission (Absolute Values) Thickness Thickness (Angstroms) nmReflectance Transmittance 0 0 0.0505 0.9495 50 5 0.1683 0.7709 100 100.3981 0.5169 150 15 0.5873 0.3264 200 20 0.7142 0.2057 250 25 0.79590.1314 300 30 0.8488 0.0851 350 35 0.8836 0.0557 400 40 0.9067 0.0368450 45 0.9222 0.0244 500 50 0.9328 0.0163 550 55 0.9399 0.0109 600 600.9448 0.0073 650 65 0.9482 0.0049 700 70 0.9505 0.0033 750 75 0.95200.0022 800 80 0.9531 0.0015

[0393] In addition to Table 2, FIG. 32 provides a graphicalrepresentation of the inverse proportion of the reflective andtransmissive nature of the thin semi-reflective layer 443 based upon thethickness of the gold. Reflective and transmissive values used in thegraph illustrated in FIG. 32 are absolute values.

[0394]FIG. 33 is a top plan view of the transmissive type opticalbio-disc 410 illustrated in FIGS. 30 and 31 with the transparent capportion 416 revealing fluidic channels 428, inlet ports 422, vent ports424, trigger marks 166, and target zones 135 as situated within thedisc.

[0395]FIG. 34 is an enlarged perspective view of optical bio-disc 410according to the transmissive disc embodiment of the present invention.Disc 410 is illustrated with a portion of the various layers thereof cutaway to illustrate a partial sectional view of each principle, layer,substrate, coating, or membrane. FIG. 34 illustrates a transmissive discformat with the clear cap portion 416, the thin semi-reflective layer443 on the substrate 420, and trigger marks 166. Trigger marks 166include opaque material placed on the top portion of the cap.Alternatively, trigger marks 166 may be formed by clear, non-reflectivewindows etched on the thin reflective layer 443 of the disc, or any markthat absorbs or does not reflect the signal coming from the triggerdetector 160 (FIG. 12). FIG. 34 also shows, the target zones 135 formedby marking the designated area in the indicated shape or alternativelyin any desired shape. Markings to indicate target zones 135 may be madeon the thin semi-reflective layer 443, on substrate 420, or on thebottom portion of the substrate 420 (under the disc). Alternatively,target zones 135 may be formed by a masking technique that includesmasking the entire thin semi-reflective layer 443 except the targetzones 135. In this embodiment, target zones 135 may be created by silkscreening ink onto the thin semi-reflective layer 443. An active layer444 is applied over the thin semi-reflective layer 443. In one preferredembodiment, active layer 444 is a thick layer of 2% polystyrene.Alternatively, polycarbonate, gold, activated glass, modified glass, ormodified polystyrene such as polystyrene-co-maleic anhydride, may beused. In addition hydrogels can be used. As illustrated in thisembodiment, adhesive or channel layer 418 is applied over active layer444. The exposed section of the adhesive layer 418 illustrates the cutout or stamped U-shaped form that creates fluidic circuits 428. Thefinal principle structural layer in this transmissive embodiment of thepresent bio-disc 410 is the clear, non-reflective cap portion 416 thatincludes inlet ports 422 and vent ports 424.

[0396] Referring back to FIG. 12, in the case of the reflective bio-discillustrated in FIG. 29, the return beam 139 is reflected from thereflective surface 446 (see FIG. 35) of cap portion 416 of the opticalbio-disc 410. In this reflective embodiment of the present opticalbio-disc 410, the return beam 139 is detected and analyzed, for thepresence of signal elements or agents, by a bottom detector 18 such asthat illustrated in FIG. 1. This reflected return beam eitheralternately or simultaneously carries both operational information andinformation characteristic of the bio-bit, signal element, orinvestigational feature. In the transmissive bio-disc format, on theother hand, the transmitted beam 162 is detected, by a top detector 160,and is also analyzed for the presence of signal agents. In thetransmissive embodiment, a photo detector may be used as top detector160. The hardware triggering mechanism may be used in both reflectivebio-discs (FIG. 29) and transmissive bio-discs (FIG. 34).

[0397]FIG. 35 is a partial cross sectional view of the reflective discembodiment of optical bio-disc 410 according to the present invention.FIG. 35 illustrates substrate 420 and reflective layer 442. As indicatedabove, reflective layer 442 may be made from a material such asaluminum, gold or other suitable reflective material. In thisembodiment, the top surface of substrate 420 is smooth. FIG. 35 alsoshows active layer 444 applied over reflective layer 442. Target zone135 is formed by removing an area or portion of reflective layer 442 ata desired location or, alternatively, by masking the desired area priorto applying reflective layer 442. As further illustrated in FIG. 35,adhesive layer 418 is applied over active layer 444. FIG. 35 also showscap portion 416 and reflective surface 446 associated therewith. Thuswhen cap portion 416 is applied to adhesive layer 418, which includesthe desired cut-out shapes, flow channels 430 are thereby formed.Incident beam 137 is initially directed toward substrate 420 from belowdisc 410, and then focused at a point proximate to reflective layer 442.Since this focusing takes place in target zone 135 where a portion ofreflective layer 442 is absent, incident beam 137 continues along a paththrough active layer 444 and into flow channel 430. Incident beam 137then continues upwardly traversing through flow channel 430 toeventually fall incident onto reflective surface 446. At this point,incident beam 137 is returned or reflected back along the incident pathand thereby forms the return beam 139.

[0398]FIG. 36 is a partial cross sectional view of the transmissiveembodiment of bio-disc 410 according to the present invention. FIG. 36illustrates a transmissive disc format with clear cap portion 416 andthin semi-reflective layer 443 on substrate 420. FIG. 36 also showsactive layer 444 applied over thin semi-reflective layer 443. In apreferred embodiment, the transmissive disc has thin semi-reflectivelayer 443 made from a metal such as aluminum or gold approximately100-300 Angstroms thick and does not exceed 400 Angstroms. This thinsemi-reflective layer 443 allows a portion of incident or interrogationbeam 137, from light source 19 (FIG. 1), to penetrate and pass upwardlythrough the disc to be detected by top detector 160 (FIG. 12), whilesome of the light is reflected back along the same path as the incidentbeam but in the opposite direction. In this arrangement, the return orreflected beam 139 is reflected from semi-reflective layer 443. Thus inthis manner, return beam 139 does not enter into flow channel 430. Thereflected light or return beam 139 may be used for tracking incidentbeam 137 on pre-recorded information tracks formed in or on thesemi-reflective layer 443 as described in more detail in conjunctionwith FIGS. 37 and 38. In the disc embodiment illustrated in FIG. 36, adefined target zone 135 may or may not be present. Target zone 135 maybe created by direct markings made on thin semi-reflective layer 443, oron substrate 420. These markings may be created using silk screening orany equivalent method. In the alternative embodiment where no physicalindicia are employed to define a target zone, flow channel 430 isutilized as a confined target area in which inspection of aninvestigational feature is conducted.

[0399]FIG. 37 is a cross sectional view taken perpendicular to thetracks of the reflective disc embodiment of bio-disc 410 according tothe present invention. This view is also taken longitudinally along aradius of a flow channel 430 of the disc. FIG. 37 includes substrate 420and reflective layer 442. In this embodiment, substrate 420 includes aseries of grooves 118, as best illustrated in FIG. 3. Grooves 118 are inthe form of a spiral extending from near the center of the disc towardthe outer edge. Grooves 118 are implemented so that interrogation beam137 may track along the spiral grooves 118 on the disc. A raised orelevated portion 110 (FIG. 3) separates adjacent grooves 170 in thespiral. The reflective layer 442 applied over grooves 118 in thisembodiment is, as illustrated, conformal in nature. FIG. 37 also showsactive layer 444 applied over reflective layer 442. Target zone 135 isformed by removing an area or portion of reflective layer 442 at adesired location or, alternatively, by masking the desired area prior toapplying reflective layer 442. As further illustrated in FIG. 37,adhesive layer 418 is applied over active layer 444. FIG. 37 also showscap portion 416 and the reflective surface 446 associated therewith.Thus, when cap portion 416 is applied to adhesive layer 418, whichincludes the desired cut-out shapes, flow channel 430 is thereby formed.

[0400]FIG. 38 is a cross sectional view taken perpendicular to thetracks of the transmissive disc embodiment of bio-disc 410 according tothe present invention. This view is also taken longitudinally along aradius of a flow channel 430 of the disc. FIG. 38 illustrates thesubstrate 420 and the thin semi-reflective layer 443. Thinsemi-reflective layer 443 allows a portion of the incident orinterrogation beam 137, from light source 19 (FIGS. 1 and 12), topenetrate and pass through the disc to be detected by top detector 160,while some of the light is reflected back in the form of return beam139. The thickness of thin semi-reflective layer 443 is determined bythe minimum amount of reflected light required by the disc reader tomaintain its tracking ability. In this embodiment, substrate 420, likethat discussed in FIG. 37, includes the series of grooves 118. Grooves118 in this embodiment are also preferably in the form of a spiralextending from near the center of the disc toward the outer edge.Grooves 118 are implemented so that interrogation beam 137 may trackalong the spiral. FIG. 38 also shows active layer 444 applied over thinsemi-reflective layer 443 with adhesive layer 418 applied overactivelayer 444. FIG. 38 also shows cap portion 416 without a reflectivesurface 446. Thus, when cap portion 416 is applied to adhesive layer418, which includes the desired cut-out shapes, flow channel 430 isthereby formed and a part of incident beam 137 is allowed to passtherethrough substantially unreflected.

[0401]FIG. 39 is a view similar to FIG. 35 showing the entire thicknessof the reflective disc and the initial refractive property thereof. FIG.40 is a view similar to FIG. 36 showing the entire thickness of thetransmissive disc and the initial refractive property thereof. Grooves118 are not shown in FIGS. 39 and 40 since the sections are cut alonggrooves 118. FIGS. 39 and 40 show narrow flow channel 430 situatedperpendicular to the grooves 118 in these embodiments. FIGS. 37, 38, 39,and 40 show the entire thickness of the respective reflective andtransmissive discs. In these figures, incident beam 137 is illustratedinitially interacting with substrate 420 which has refractive propertiesthat change the path of the incident beam as illustrated to providefocusing of beam 137 onto the reflective layer 442 or the thinsemi-reflective layer 443.

[0402] Optimizing the Optical Bio-Disc

[0403] A disc is optimized to provide a surface for detection ofmicroscopic structures in an optical disc system. An optical disc iscreated for use in the optically corrected player previously discussed.The disc is manufactured as the “reverse image” or the forward image ofa CD-Recordable disc, for example. Such optical discs and relatedmanufacturing methods are further disclosed in commonly assigned U.S.patent application Ser. No. 10/005,313 entitled “Optical Discs forMeasuring Analytes” filed Dec. 7, 2001, which is herein incorporated byreference. One such disc is the disc 130 illustrated in FIG. 41implemented as a “reverse wobble” disc. This embodiment of the disc 130,includes the disc substrate 132 “reversed” as illustrated to form thecap or most distal layer. The disc further includes grooves 118 withbio-bits, signal elements, or investigation features 136 preferablysituated therein. A non-integral cover 138 is then utilized as aproximal cap as shown relative to the incident beam 137.

[0404] In the Compact Disc Recordable (CD-R) System, a laser is focusedthrough a 1.2 mm polycarbonate (or similar refractive material) and isfocused on a groove-like structure filled with dye materials that haveabsorption-effective properties. The disc manufactured for use in thisdetection system is manufactured as the “reverse image” of a CD-R disc.The reverse image allows the optical disc reader to interface with thefirst surface or air-interface of a continuous groove. The air-interfaceallows for a process that places microscopic structures on the surfacethat can be read.

[0405] The disc is manufactured using an electroforming or “NickelStamper” production method referred to as “Matrixing.” Once a nickelimage has been created from the surface of an optical disc “Master,” itcan be placed in an electroforming process (or similar process) and areverse image can be created. The “Master” is often called the “Father”part. The “reverse image part” is often called the “Mother” part. Inmany CD manufacturing processes, the “Mother” part is used to produceanother reverse image that is called the “Son” part. “Father” parts and“Son” parts have the same forward image. “Mother” parts have the reverseimage. This process allows a master made from a normal CD-Recordablemastering process to be used for this application. It is technicallyfeasible and possible to create “Father” parts with the correct forwardimage for this disc. The reverse image part is made of nickel and isutilized in an optical disc molding machine to create a plastic partrepresenting the opposing image.

[0406] The reverse image part is more difficult to utilize in a CDmanufacturing process because of its geometry. The edge of a forwardimage part is open and the edge of a reverse image part is closed. Amold must be designed for the CD molding process. This mold is providedwith additional vents that allow the movement of polycarbonate or otherremoldable refractive material to move properly across the surface ofthe nickel part. The venting design added to the mold will allow thedesired optical discs to be created in a fashion similar to compactdiscs or CD-R discs.

[0407] The desired optical disc is designed with an optimized shape andform of the structure of a continuous groove that originates at theinner diameter and ends at the outer diameter of the disc. The groovedepth is optimized to provide a very strong tracking magnitude(push-pull signal). The depth of the manufactured groove is very closeto {fraction (1/8)} of the wavelength λ of the laser light incident onthe air interface of the optical disc. The depth of the manufacturedgroove can also be odd multiples of these values (e.g., {fraction(1/8)}λ, {fraction (3/8)}λ, {fraction (5/8)}λ, etc.). The width of theoptical disc groove is optimized to facilitate placement or sizedetection of the structures that will be placed on the surface of theoptical disc. Thus in one preferred embodiment, a {fraction (1/8)} wavepush-pull tracking derivation is employed. The slope of the groovestructure is optimized to provide for an optimal focusing position inthe groove and for an optimized tracking signal response. Optimizationof the land areas within the continuous groove is performed to reducesignal cross-talk and to optimize structure detection.

[0408] The air-incident surface of the optical disc is manufactured toprovide light contrast to the microscopic structures that will be placedon the surface of the disc. If the structures absorb light, a reflectivematerial (such as gold) is placed on the air-incident surface. If thestructures reflect light, a non-reflective material will be placed onthe air-incident surface. The discs are manufactured to provide optimalmechanical performance in a CD recordable player.

[0409] The air-incident surface of the reverse image disc provides therequired operational requirements of the optically corrected playerdiscussed previously. The adjustment lens will allow the reverse imagedisc to perform similarly to a non-recorded CD-R disc. This test mode isavailable through the software interface of a consumer CD-R drive. Theplayer can be placed in a test mode and will track the “wobbled” groovethrough the information area. The location of a component on the surfaceof the wobbled groove can be detected to {fraction (1/75)} of a secondby utilizing the consumer CD-R wobbled groove format. The locationalinformation in the consumer CD-R format is contained in the mastered“wobble” signal and can be secured through the software interface to aconsumer drive. Microscopic structures placed on the surface of thereverse image disc will not have an effect on the operationalrequirements of a wobble groove system until they reach a very highconcentration (point of data gathering). In effect, the wobble grooveallows for placement of microscopic structures on the surface of theoptical disc without having an adverse effect on the operationalrequirements of the CD-R system.

[0410] The characteristics of the structures placed on the surface ofthe reverse image disc can now be detected by monitoring the quad sumsignal of the CD-R objective assembly. The electrical response of thesemicroscopic structures can also be detected in the electrical signalapplied to the focusing servo, the tracking servo, and the power controlmonitoring system. The characteristics of the head movement in theradial and tangential plane parallel to the surface of the reverse imagedisc can be detected in the electrical signal applied to the trackingservo circuitry. The characteristics of the head movement in thevertical plane perpendicular to the surface of the reverse image disccan be detected on the electrical signal applied to the focusing servocircuitry. These signals can be cross-referenced to the informationgathered by the quad sum signal and the power-monitoring signal. Theinformation for each of these responses can be analyzed in amathematical format to relate dimensional characteristics of themicroscopic structure detected on the surface in the reverse image disc.An application of Differential Mathematics or Vector analysis can beapplied to extract the characteristics of each microscopic structure.

[0411] Structures on the surface of the reverse image disc can bedesigned for maximum detection resolution by designing a placement anddimensional requirement to remain within the focal position of the laserspot. The microscopic structures should be designed for maximal opticalcontrast with the surface of the reverse image disc to provide forstrong signal detection and low electrical CNR. Microscopic structuresapplied to the surface of the reverse image disc should be small enoughto remain within the focusing plane of the laser spot. As thedimensional characteristics overcome the focal position, a smallerportion of the signal is detected in the quad sum detector, while alarger portion of the signal is detected in the other operationalservos.

[0412] The disc may be designed with a specialty groove that wouldaccommodate the dimensional aspects of the microscopic structures. Themicroscopic structures can be designed for placement inside the groovesof the reverse image disc. This would be used to further optimize thequantifiable detection characteristics of the system. The microscopicstructures are created in a “spherical shape.” These spheres, whenplaced on the surface of the reverse image disc, generate a verycharacteristic electrical response in the servo and operational signalsin the drive. The land areas of the disc (the areas between the grooves)are created with a smooth round surface, which will allow the spheres tofall into a holding position within the groove that is easily detectedby the electrical signals.

[0413] The reporter spheres or bio-bits may be created with a diameterthat is smaller than the width of the groove as discussed above. Thisallows the spheres to enter the groove and facilitates detection asrepresented in FIG. 41. The spheres can also be formed out of acompressible material and have a diameter that is slightly larger thanthe width of the groove. In one embodiment, an adaptable plate is usedto compress the spheres and drive them into the groove.

[0414] Having described certain embodiments, it should become apparentthat modifications could be made without departing from the scope of theclaims as set out below. For example, the terms over and under are usedfor reference purposes and not absolute positioning.

[0415] Investigational Features

[0416] The structures, features, characteristics, and attributes thatare investigated according to the present invention may includebiological, chemical, or organic specimens, test samples,investigational objects such as parts of insects or organic material,and similar test objects or target samples. Such structures, features,and attributes may also, include specific chemical reactions and theproducts and/or by-products resulting therefrom such as, for example,any one of a variety of different colorimetric assays. In the case of anoptical bio-disc, the material applied to the disc for investigation andanalysis may include biological particulate suspensions and organicmaterial such as blood, urine, saliva, amniotic fluid, skin cells,cerebrospinal fluid, serum, synovial fluid, semen, single-stranded anddouble-stranded DNA, pleural fluid, cells from selected body organs totissue pericardial fluid, feces, peritoneal fluid, and calculi. In thecase of some of these materials, a reporter may be employed fordetection purposes. Reporters useful in the invention described hereininclude, but are not limited to, plastic micro-spheres or beads made of,for example, latex, polystyrene, or colloidal gold particles withcoatings of bio-molecules that have an affinity for a given materialsuch as a biotin molecule in a strand of DNA. Appropriate coatingsinclude those made from streptavidin or neutravidin, for example. Inthis manner, objects too small to be detected by the read beam of thedrive may still be detected by association with the reporter.

[0417] An optical disc playback device can be used to detect featuresand surface characteristics in the focusing plane of an optical disc.Microscopic structures, cells, reporters, or “bio-bits” are added to afocusing plane in the optical disc assembly so that they can be detectedin the electrical signals that are generated when the laser lightreflected or transmitted from the surface of the optical disc iscollected by the objective assembly and/or a top detector. Themicroscopic structures and the optical disc platform are designed topromote accurate detection and to have a minimal effect on theoperational requirements of the system.

[0418] Small biological and/or spherical structures are measured on thesurface or within the focusing planes described as follows. Thesestructures are physically larger than one-half the wavelength of thelight used to detect them (the light incident on the structures).

[0419] When these microscopic structures or bio-bits exist on thesurface of the optical disc focal plane, the structures will appear onthe surface of the land areas. Signal elements, bio-bits, orinvestigational features may also exist on a plane that is not withinthe immediate field of focus but is very near. In this case, thestructures are close enough to the field of focus to be detectable bythe reflected laser light. Investigational features such as bio-bits canalso exist on multiple planes that are separated from the laser that isfulfilling the operational requirements of characterization of thestructures. The bio-bits and other reporters may also be inserted intothe groove or pits and cause enough optical interference in thereflected signal to generate a confident detection signal. Bio-bits canalso exist within areas that are logically zoned or organized by themanufacturing of the disc. These areas may be land-level or pit-level,and may be very large (e.g., DVD-RAM).

[0420] Detecting Investigational Features

[0421] Investigational features, such as reporters or blood cells,produce a signal level or density change relative to a signal producedby reading information encoded on the disc. Commonly assigned andco-pending U.S. patent application Ser. No. 09/421,870 entitled“Trackable Optical Discs with Concurrently Readable NonoperationalFeatures” filed Oct. 26, 1999, herein incorporated by reference, teachesthat micron-sized investigational or “non-operational” structures may bedisposed upon a surface of an optical disc in a number of ways. Onesuitable embodiment for accomplishing this is depicted in FIG. 41 asdiscussed above. As shown in FIG. 41, light beam 137 is incident uponthe disc assembly 130 from below. Disc 130 includes disc substrate 132and reflective layer 134, upon which investigational structures orfeatures 136 are disposed. Wobble grooves 118, impressed in substrate132 and coated by reflective layer 134, are indicated in FIG. 41. Alsoshown is the non-integral cover 138. Investigational structures 136 maybe detected, measured, and characterized by the optical disc readeraccording to the present invention. The operational structures of thedisc, including tracking features, may be detected concurrently (ornon-concurrently) with, and readily discriminated from, investigationalstructures using a single optical pickup.

[0422] With reference next to FIG. 42, a view similar to FIG. 5discussed above, there is shown three light spots that are produced by atypical three-beam optical design incident on an optical disc assemblyhaving pits 60. Laser beam spots 62, 64, and 66 are illustrated asdashed lines on the surface of the optical disc. These beams can befocused on the same surface of the disc as pits 60, or on any otherouter surface or inner surface of the disc. These beams can also befocused on different layers of the disc, a “layer” referring to anyportion of the disc that has a finite thickness such as in themulti-layer discs disclosed in U.S. patent application Ser. No.10/006,620 referenced above.

[0423] In a three-beam optical disc system, detectors A, B, C, and D, asshown in FIG. 4, are configured to detect light reflected from beam spot62, as shown in FIG. 42. Also, detectors E and F are independentlyconfigured to detect the reflected light from beam spots 64 and 66,respectively. As mentioned above, this configuration has beenimplemented such that focus and synchronization information are providedby light reflected at beam spot 62 and the tracking information isprovided by light reflected at beam spots 64 and 66.

[0424]FIG. 43 shows an investigational feature 68 disposed on a surfaceof an exemplary optical disc assembly. In this arrangement, beam spot 62can be used to detect operational structures (e.g., pits) for tracking,focus, and synchronization and beam spot 66 can be used simultaneouslyto detect one or more investigational features 68. Alternatively, beamspot 64 may be used to detect investigational feature 68, depending onthe size and location of investigational feature 68.

[0425] Also, if investigational feature 68 is sufficiently large, beamspots 64 and 66 can be used in combination (though not necessarilysimultaneously) for detecting investigational feature 68. It will beappreciated that a combination of patterns from each of the beam spotscan be used to detect the size and position of investigational feature68. Also, patterns from detectors A, B, C, and D can be combined withpatterns from one or both of detectors E and F to determine the size andposition of the investigational features. Thus, a single objectiveassembly can detect different optical paths of operational structuresand investigational features. It will be appreciated that the inventiondisclosed herein relates to the detection of operational andinvestigational features and is not limited to an optical disc assemblyhaving a pits and lands format. Rather, the invention can be used withany other format such as those discussed above.

[0426]FIG. 44 is a graph illustrating a representative relativedisplacement of the data signal (or density) when the read beam of thedrive encounters such an investigational feature on or in the disc. Thedata signal may be the HF signal, the tacking error signal, the focuserror signal, or one or more of a variety of other different signalssuch as those identified above.

[0427] In FIGS. 45 and 46, a change in an “operational” feature such asa groove, pit or land, produces a change in signal level, signal jitter,or error rate. In FIG. 45, a section view of a pit, the pit produces achange in signals A and B from the detector of the disc reader, and,when added, an unusual fluctuation is produced. In FIG. 46, a plan viewof a pit, a lateral displacement produces a net displacement in thetracking error signal (TE signal).

[0428] An increase or decrease in reflectivity is produced when theincident beam interacts with the disc. This change in reflectivity canbe monitored by a corresponding change in the Automatic Gain Control(“AGC”) setting, which is output at the drive port. Thus, in accordancewith the present invention, when the read or “interrogation” beam of thedrive encounters an investigational feature, a change in return light ismonitored.

[0429] The structure of an optical disc can be anything from a surfacewith pits and lands, a surface with a continuous wobbled groove, asurface containing a phase contrast hologram, a surface with acombination of pits/grooves or a surface with nothing on it. Asdiscussed previously, reporters, bio-bits, or cellular structures can bemeasured in many different focusing planes. Bio-bits can also bedetected and characterized by multiple lasers, multiple objectiveassemblies, and multiple laser wavelengths.

[0430] Reporters, bio-bits, and cellular structures could be located onthe primary surface of a holographic disc. Further details relating tothis use of holograms is disclosed in U.S. patent application Ser. No.10/005,313. The information gathered from the hologram is used foroperational characteristics. Bio-bits can be put as close to or as faraway from the operational plane as needed. The refractive layer(polycarbonate, polymethyl acrylic or glass) can be adjusted to optimizethe desired optical properties of the detection laser.

[0431] Alternatively, investigational features may include a chemicalreaction, taking place in a flow channel, such as flow channel 430 shownin FIG. 27, formed on or in the disc as illustrated in FIG. 47. In thisembodiment, the reflectivity, operational features, or interferencepatterns on an optical disc are affected by a chemical deposition orreaction. The disc is manufactured with a very low error rate or a knownerror rate that acts as a data “mask.” The data pattern on the disc isdesigned to produce a logical or physical enhancement to the errorsproduced by investigational features or groupings of a specific sizerange.

[0432] For example, the interleaving distance can be adjusted in themastering logic to enhance the burst error response to a specificfeature, size, or density distribution. A data pattern is written on thedisc to produce as a response to specific feature sizes or densitydistribution. These may include, but are not limited to, the following:

[0433] 1. a non-pause;

[0434] 2. a sound signal (response to digital silence encoding);

[0435] 3. a specific error correction pattern or distribution (e.g.,E11, E21, E31, burst, E12, E22, E32, E42);

[0436] 4. an uncorrectable error;

[0437] 5. an ECC/EDC count;

[0438] 6. an inner or outer parity error;

[0439] 7. a CRC error in the wobble signal decoder;

[0440] 8. a sector error (75/sec); or

[0441] 9. a block error (7350/sec).

[0442] In an exemplary embodiment, a fluidic channel is placed within adisc. The disc can have up to 99 tracks with grooves, pits, or acombination of operational features for CD, CD-R, DVD, DVD-RAM, DVD-R,DVD-RW. A specific chemical reaction or deposition of “non-ops”(spheres, metallics, etc.) will enhance or remove material from themetallic reflective layer or the operational or focal plane. Spots orzones are placed on the disc in different bands or tracks. Logic in eachband determines the position of the objective assembly. Logic can alsodetermine the “software servo response.” Starting with low-densitydistribution or effect, spots are placed in increasing density andincreasing radius positions in each bank or track. On a DVD-RAM disc orsimilar, the spots are placed within the Zones (Zoned CLF system). Thereaction will produce physical changes in the “ops features,” inducingerrors or error sites on the disc at each location. The digital, analog,optical, mechanical, and logical responses may be evaluated tocharacterize the effect.

[0443] In this embodiment, each site has increasing error rates and anattempt is made to correlate to the error distributions: E11, E21, E31,Burst, E12, E22, E32, E42, Uncorrectable, Unrecoverable, ECC/EDC, orBLER. In a preferred embodiment, the process is started with low-densitydistributions and moved to higher distributions until a correlation isdiscovered between the analyte concentration and the error distribution.The disc is advantageously mastered to enhance the correlation. Forexample, interleaving is modified or changed to enhance the Burst and C2response.

[0444] Reaction with the surface, operational plane, or focal plane ofthe disc creates and increases or decreases analog signal level ordensity. The reaction will produce a change in reflectivity or signaldensity, either a reduction or increase in reflective layer, or a changein shape and/or size of phase/interference features (pits or lands).

[0445] As a general proposition, the reflectivity of a metal layer is afunction of the thickness of the layer up to a certain thresholdthickness as discussed above in connection with FIG. 32. For a varietyof different metals such as nickel, aluminum, silver, or gold, asrepresented in FIG. 48, reflectivity is unchanging and remainsessentially constant at between about 80% and nearly 100% for a metalthickness equal to or greater than a threshold thickness. Thisreflectivity also depends on metal purity and surface conditions. As ageneral matter relating to certain specific aspects of the presentinvention, a metal film thickness and surface condition can be alteredwhen a metal film such as reflective layer 443 (as best illustrated inFIG. 34) reacts with a fluid contained in flow channels of the disc.

[0446] In FIG. 49, the chemical reaction occurring in the flow channel430 of the disc illustrated in FIG. 47 causes fluctuations in signalsbeing monitored, for example, the HF or TE signal. When theinterrogation beam 137 of a disc drive traverses across a chemicalreaction occurring in or on the disc, the envelope of the signalfluctuations increases or decreases with reaction time.

[0447] According to another aspect of the present invention, pits,marks, or grooves on a disc can be made of a chemically interactivematerial. The level of degradation in the material can determine someassay characteristics by providing a change in signal response.Chemistry or assay material can react with the reflective layer andreduce or enhance light transmitted, reflected, refracted, or absorbedaccording to the change in reflectivity of the reflective or metal layer443 shown in FIG. 47. For example, operational structures may be made ofa nitrated cellulose material. Chemical interactions may change theshape and/or thickness of operational structures, and thus, reducesignal response. Also the pH of the solution may cause a deposition ofmetal on the surface of a zone in the disc and produce an increase inlocalized reflectivity. In another implementation, localized reactionsmay cause the removal of metallic material from the reflective surface.The removal of the material will cause a point of contrast in thesignal. The response may be an analog signal characterization or anerror rate distribution. Additionally, zones may be designed into thedisc for differing concentrations and reactions. In these embodiments,the material is designed in such a way as to degrade at a specificconcentration or reaction level.

[0448]FIG. 50 generally represents these aspects of the presentinvention. The disc in FIG. 50 includes zones A, B, and C that areformed, for example, on a DVD-RAM disc with Zoned Constant LinearVelocity, (ZCLV). Zone C included a reaction according to this aspect ofthe present invention where the reflective layer was removed, while inzones A and B no such metal-removing reaction occurred. The resultingsignal traces of, for example, the HF or TE signals are also shown. Thesignal traces reveal that traces across the zones with the reflectivematerial intact generated a detectable signal, while the scan across thezone without reflective material did not.

[0449] With reference now to FIG. 51, there is shown a cross-sectionalside view of an optical bio-disc 200 that includes bead reporters 210 asutilized in conjunction with the present invention. Bio-disc 200includes substrate 202, metal film layer 204, an adhesive or channellayer 206, and cover disc 208. Substrate 202 includes pits or groves orother means on which information may be encoded in known ways. Substrate202 is generally covered with metal film layer 204 in areas over whichinformation is encoded. However, bio-disc 200 differs from knowninformation discs (e.g., music, DVD, etc.) in that the bio-disc includesan investigational structure (in this case bead reporters) over a partof the disc. Chemical layer 214 (e.g., antibodies) is deposited in adesired target area of the disc. Each bead reporter 210 also has asurface coated with a similar or identical chemical layer 212. The beadreporters 210 are small plastic spheres (or other material spheres) thatare coated with a chemical agent to interact with biological chemicalsin a solution.

[0450] As a specific example of one aspect of the present invention,FIG. 52A presents a graphical representation of two 6.8 μm blue beadspositioned relative to several tracks (labeled A through H) of anoptical bio-disc according to this invention. These beads were locatedon and adhered to a disc similar to the disc shown in FIG. 51. Scantraces A through H are depicted, several of which pass over the beadreporters.

[0451]FIG. 52B is a series of signature traces including distinctivesignal perturbations derived from the bead reporters of FIG. 52Autilizing an AC coupled and buffered HF signal from the optical driveaccording to the present invention. The HF-AC coupled signal from HFMatrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.52B reveals that a scan over two 6.8 μm reporter beads results indistinct perturbations of the HF signal that can be detected.

[0452] As another particular example, FIG. 53A presents a graphicalrepresentation of two 6.42 μm red beads positioned relative to thetracks of an optical bio-disc according to the present invention. Thesebeads were located on a disc similar to the disc shown in FIG. 51.

[0453]FIG. 53B is a series of signature traces derived from the beads ofFIG. 53A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention. The HF-AC coupled signal fromHF Matrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to an ADC 150 and is processed by PC 158 and imaged bydisplay 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.53B reveals that a scan over two 6.42 μm reporter beads results indistinct perturbations of the HF signal that can be detected.

[0454] As yet another example according to the present invention, FIG.54A presents a graphical representation of two 6.33 μm polystyrene beadspositioned relative to the tracks of an optical bio-disc according tothe present invention. These beads were located on a disc similar to thedisc shown in FIG. 51.

[0455]FIG. 54B is a series of signature traces and related signalperturbations derived from the beads of FIG. 54A utilizing an AC coupledand buffered HF signal from the optical drive according to the presentinvention. The HF-AC coupled signal from HF Matrix Amp 18A (FIG. 21) ofoptical head assembly 174 (FIG. 19) is directed to buffer amplifier card152 (see FIGS. 22 and 23). The signal is amplified and conditioned (FIG.24B) then directed to output connector J3 of output section 157 (FIG.22). From buffer amplifier card 152, the signal is sent to an ADC 150and is processed by PC 158 and imaged by monitor 146 (see FIGS. 9A and12). As described above, modified PC 142 may substitute one or more ofthe processing devices described herein. FIG. 54B reveals that a scanover two 6.33 μm polystyrene reporter beads results in distinctperturbations of the HF signal that can be detected.

[0456] As yet still another example of certain aspects of the presentinvention, FIG. 55A presents a graphical representation of a 5.5 μmglass reporter bead positioned relative to the tracks of an opticalbio-disc according to this invention. This bead was located on a discsimilar to the disc shown in FIG. 51.

[0457]FIG. 55B is a series of signature traces derived from the beadillustrated in FIG. 55A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed tooutput connector J3 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 55B reveals that a scan over a 5.5 μm glassreporter bead results in a perturbation of the HF signal that can bedetected.

[0458] Another example of this invention is presented in FIG. 56A whichshows a graphical representation of a 4.5 μm magnetic bead positionedrelative to the tracks of an optical bio-disc according to the presentinvention. This bead was located on a disc similar to the disc shown inFIG. 51.

[0459]FIG. 56B is a series of signature traces derived from the beadillustrated in FIG. 56A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed tooutput connector J3 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 56B reveals that a scan over a 4.5 μm magneticreporter bead results in a perturbation of the HF signal that can bedetected.

[0460]FIG. 57A is a graphical representation of two actual 4.0 μm bluebeads positioned relative to the tracks of an optical bio-disc accordingto another example of certain aspects of the present invention. Thesebeads were located on a disc similar to the disc shown in FIG. 51.

[0461]FIG. 57B is a series of signature traces and related signalperturbations derived from the beads of FIG. 57A utilizing an AC coupledand buffered HF signal from the optical drive according to the presentinvention. The HF-AC coupled signal from HF Matrix Amp 18A (FIG. 21) ofoptical head assembly 174 (FIG. 19) is directed to buffer amplifier card152 (FIGS. 22 and 23). The signal is amplified and conditioned (FIG.24B) then directed to output connector J3 of output section 157 (FIG.22). From buffer amplifier card 152, the signal is sent to ADC 150 andis processed by PC 158 and imaged by monitor 146 (FIGS. 9A and 12). Asdescribed above, modified PC 142 may substitute one or more of theprocessing devices described herein. FIG. 57B reveals that a scan overtwo 4.0 μm reporter beads results in a perturbation of the HF signalthat can be detected.

[0462] As yet a further example hereof, FIG. 58A shows a graphicalrepresentation of a 2.986 μm polystyrene bead positioned relative to thetracks of an optical bio-disc according to the present invention. Thisbead was located on a disc similar to the disc shown in FIG. 51.

[0463]FIG. 58B is a series of signature traces derived from the beadillustrated in FIG. 58A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed tooutput connector J3 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 58B reveals that a scan over a 2.986 μmpolystyrene reporter bead results in a perturbation of the HF signalthat can be detected.

[0464] An yet still as a further example of this invention, FIG. 59Apresents a graphical representation of two 2.9 μm white beads positionedrelative to the tracks of an optical bio-disc according to the presentinvention. These beads were located on a disc similar to the disc shownin FIG. 51.

[0465]FIG. 59B is a series of signature traces derived from the beads ofFIG. 59A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention. The HF-AC coupled signal fromHF Matrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.59B reveals that a scan over two 2.9 μm reporter beads results indistinct signal perturbations of the HF signal that can be detected.

[0466]FIG. 60A is a graphical representation of four 2.8 μm magneticbeads positioned relative to the tracks of an optical bio-disc accordingto another specific example of certain aspects of this invention. Thesebeads were located on a disc similar to the disc shown in FIG. 51.

[0467]FIG. 60B is a series of signature traces derived from the beads ofFIG. 60A utilizing an AC coupled and buffered HF signal from the opticaldrive according to the present invention. The HF-AC coupled signal fromHF Matrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.60B reveals that a scan over four 2.8 μm magnetic reporter beads resultsin distinct perturbations of the HF signal that can be detected.

[0468] As another example, FIG. 61A presents a graphical representationof a mixture of beads including 2.8 μm magnetic beads, 4.0 and 6.8 μmblue polystyrene beads, and different sized silica beads positionedrelative to the tracks of an optical bio-disc according to the presentinvention. These beads were located on a disc similar to the disc shownin FIG. 51.

[0469]FIG. 61B is a series of signature traces and related signalperturbations derived from the beads of FIG. 61A utilizing an AC coupledand buffered HF signal from the optical drive according to the presentinvention. The HF-AC coupled signal from HF Matrix Amp 18A (FIG. 21) ofoptical head assembly 174 (FIG. 19) is directed to buffer amplifier card152 (FIGS. 22 and 23). The signal is amplified and conditioned (FIG.24B) then directed to output connector J3 of output section 157 (FIG.22). From buffer amplifier card 152, the signal is sent to ADC 150 andis processed by PC 158 and imaged by monitor 146 (FIGS. 9A and 12). Asdescribed above, modified PC 142 may substitute one or more of theprocessing devices described herein. FIG. 61B reveals that a scan overthe mixture of reporter beads results in distinct perturbations of theHF signal that can be detected.

[0470]FIG. 62A is a graphical representation of two 2.9 μm whitefluorescent polystyrene beads positioned relative to the tracks of anoptical bio-disc according to the present invention. These beads werelocated on a disc similar to the disc shown in FIG. 51 and in thisexample a DC coupled signal is utilized rather than the AC coupledsignal discussed in connection with the example traces illustrated inFIGS. 52B through 61B.

[0471]FIG. 62B is a series of signature traces derived from the beads ofFIG. 62A utilizing a DC coupled and buffered HF signal from the opticaldrive according to the present invention. The HF-DC coupled signal fromHF Matrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24A) then directed to output connectorJ5 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.62B reveals that a scan over two 2.9 μm white fluorescent polystyrenebeads results in distinct perturbations of the HF-DC signal that can bedetected.

[0472]FIG. 63A is a graphical representation of two 2.9 μm whitefluorescent polystyrene beads, as illustrated in FIG. 62A, positionedrelative to the tracks of an optical bio-disc according to the presentinvention. These beads were located on a disc similar to the disc shownin FIG. 51. In this example, a DC coupled and buffered “A” signal isemployed to obtain the desired signal traces as discussed in furtherdetail immediately below.

[0473]FIG. 63B is a series of signature traces derived from the beads ofFIG. 63A utilizing the DC coupled and buffered “A” signal from theoptical drive according to the present invention. The HF-A coupledsignal (FIG. 22) from optical head assembly 174 (FIG. 19) is directed tobuffer amplifier card 152 (FIGS. 22 and 23). The signal is amplified andconditioned (FIGS. 24B and 24C) then directed to output connector J7 ofoutput section 157 (FIG. 22). From buffer amplifier card 152, the signalis sent to ADC 150 and is processed by PC 158 and imaged by monitor 146(see FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.63B reveals that a scan over two 2.9 μm white fluorescent polystyrenebeads results in distinct perturbations of the HF-A signal that can bedetected.

[0474]FIGS. 64A and 64B are the same cross-sectional side view ofoptical bio-disc 200 (FIG. 51) showing the biochemical interactionbetween the bio-disc and the reporter beads in greater detail.

[0475]FIG. 64A shows greater detail of chemical layer 214 disposed overmetal film over metal film layer 204. Chemical layer 212 is also showncoated over reporter beads 210. In FIG. 64B, the beads are mixed withthe biological solution containing investigational feature 216, andinjected into or otherwise applied to bio-disc 200 between substrate 202and cover 208. Both the chemical layer 212 on the surface of the beadreporters 210 and chemical layer 214 attract and adhere toinvestigational feature 216. In this way, if the chemical underinvestigation (i.e., investigational feature) is present in thebiological solution, the chemical under investigation becomes a bondingagent to bond the bead reporters 210 to substrate 202. When bio-disc 200is spun up, it acts like a centrifuge. Bead reporters that are notbonded will be forced to an outer periphery of the disc, and bonded beadreporters will remain uniformly distributed over the area of the disccoated with chemical layer 204. It then remains only to decide whetherthe bead reporters have been swept to an outer periphery of the disc.Examples of such bead-based assay discs and methods of use are describedin commonly assigned U.S. Provisional Applications: No. 60/257,705,titled “Surface Assembly for Immobilizing DNA Capture Probes andBead-Based Assay Including Optical Bio-Discs and Methods RelatingThereto,” filed Dec. 22, 2000; No. 60/292,110, titled “Surface Assemblyfor Immobilizing DNA Capture Probes using Pellets as Reporters inGenetic Assays Including Optical Bio-Discs and Methods RelatingThereto,” filed May 18, 2001; and No. 60/302,757, titled “ClinicalDiagnostic Optical Bio-Disc and Related Methods for Selection andDetection of Lymphocytes Including Helper-Inducer/Suppressor-CytotoxicCells,” filed Jul. 3, 2001. By the above examples, the inventors haveillustrated that discernable signals of investigational features may bereadily detected using reporter beads as described herein.

[0476]FIG. 65 is a cross-sectional side view of an optical bio-disc 190including a proximally positioned red blood cell 199 as theinvestigational feature interrogated by the read beam 191 of the opticaldisc drive assembly according to the present invention.

[0477] Bio-disc 190 includes substrate 192, metal film layer 194,adhesive or channel layer 196, and cover disc 198. Substrate 192includes pits, groves, or other means on which information may beencoded in ways known in the art. Substrate 192 is generally coveredwith metal film layer 194 in areas over which information is encoded.However, bio-disc 190 differs from known information discs (e.g., music,DVD, etc.) in that the bio-disc includes an investigational structure(in this case, a blood cell 199) over a part of the disc. Metal filmlayer 194 is removed from areas to be used for investigationalstructures. Capture agent 195 (e.g., antibodies) is deposited in thearea of the removed metal film layer. Blood cell 199 may include abiological chemical under investigation (e.g., a chemical unique forblood type A or type B) that has an affinity for capture agent 195. Inthis way, if the chemical under investigation is present in thebiological specimen, the chemical under investigation becomes a bindingagent to bind blood cell 199 to substrate 192. When bio-disc 190 is spunin an optical disc drive, the resulting centrifugal force sends bloodcells that are not bound to an outer periphery of the disc, while boundblood cells remain distributed over the area of the disc coated withcapture agent 195. The bound cells are then detected and quantifiedusing an optical disc reader. Further details relating to this type ofon-disc blood typing assays are disclosed in commonly assigned,co-pending U.S. patent application Ser. No. 09/988,850 entitled “Methodsand Apparatus for Blood Typing with Optical Bio-Discs” filed Nov. 19,2001, which is herein incorporated by reference.

[0478] As an example of detection of a cell reporter according tocertain aspects of the present invention, FIG. 66A presents a graphicalrepresentation of proximally positioned red blood cell 199,approximately 6.0 μm in diameter, positioned relative to the tracks ofthe optical bio-disc 190 illustrated in FIG. 65.

[0479]FIG. 66B is a series of signature traces derived from the redblood cell of FIG. 66A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed tooutput connector J3 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 66B reveals that a scan over a proximallypositioned red blood cell results in a perturbation of the HF-AC coupledsignal that can be detected.

[0480]FIG. 67A is a graphical representation of a proximally positionedred blood cell approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to the present invention.For this example, the red blood cell illustrated in FIG. 67A was locatedon the type of the disc shown in FIG. 65.

[0481]FIG. 67B is a series of signature traces derived from the redblood cell of FIG. 67A utilizing a DC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-DCcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24A) then directed tooutput connector J5 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 67B reveals that a scan over a proximallypositioned red blood cell results in a perturbation of the HF-DC signalthat can be detected.

[0482]FIG. 68 is a cross-sectional side view of an optical bio-disc 190similar to the disc shown in FIG. 65, including a distally positionedred blood cell 199 as the investigational feature interrogated by readbeam 191 of the optical disc drive assembly according to the presentinvention.

[0483] Bio-disc 190 includes substrate 192, metal film layer 194,adhesive or channel layer 196, and cover disc 198. Substrate 192generally includes pits or groves or other means on which informationmay be encoded in known ways except over areas in which investigationalstructures are to be located. Substrate 192 is generally covered withmetal film layer 194 in areas over which information is encoded but notin areas in which investigational structures are to be located. Bio-disc190 differs from known information discs (e.g., music, DVD, etc.) inthat the bio-disc includes an investigational structure (in this case, ablood cell 199) over a part of the disc. Metal film layer 194 is removedfrom areas to be used for investigational structures. Capture agent 195(e.g., antibodies) is deposited in the area on cover disc 198 oppositethe removed metal film layer. Blood cell 199 may include a biologicalchemical under investigation (e.g., a chemical unique for blood type Aor type B) that is attracted to and adheres to capture agent 195. Inthis way, if the chemical under investigation is present in thebiological specimen, the chemical under investigation becomes a bindingagent to bind blood cell 199 to disc cover 198. When bio-disc 190 isspun in an optical disc drive, the resulting centrifugal force sendsunbound blood cells to an outer periphery of the disc, while bound bloodcells remain distributed over the area of the disc coated with captureagent 195. The bound cells can be detected and quantified using anoptical disc reader as further described in U.S. patent application Ser.No. 09/988,850 referenced above.

[0484]FIG. 69A is a graphical representation of two distally positionedred blood cells approximately 6.0 μm in diameter positioned relative tothe tracks of an optical bio-disc according to this example of theseaspects of the present invention. The red blood cells illustrated inFIG. 69A were located on the type of the disc shown in FIG. 68.

[0485]FIG. 69B is a series of signature traces derived from the redblood cells of FIG. 69A utilizing an AC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed toconnector output J3 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 69B reveals that a scan over two distallypositioned red blood cells results in distinct perturbations of theHF-AC coupled signal that can be detected.

[0486]FIG. 70A is a graphical representation of the two distallypositioned red blood cells illustrated in FIG. 69A. The red blood cellsillustrated in FIG. 70A were located on the type of the disc shown inFIG. 68.

[0487] As yet a further example of certain aspects of this invention,FIG. 70B presents a series of signature traces derived from the redblood cells of FIG. 70A utilizing a DC coupled and buffered HF signalfrom the optical drive according to the present invention. The HF-DCcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24A) then directed tooutput connector J5 of output section 157 (FIG. 22). From bufferamplifier card 152, the signal is sent to ADC 150 and is processed by PC158 and imaged by monitor 146 (FIGS. 9A and 12). As described above,modified PC 142 may substitute one or more of the processing devicesdescribed herein. FIG. 70B reveals that a scan over two distallypositioned red blood cell results in distinct perturbations of the HF-DCsignal that can be detected.

[0488]FIG. 71 is a top perspective view of an optical inspection disc220 with the top cap removed to illustrate a gnat's wing 222 positionedin an inspection channel 224 according to the present invention. Opticalinspection disc 220 illustrated in FIG. 71 also includes a trigger mark166. Trigger mark 166 provides the same function as the trigger mark 166discussed in detail in conjunction with FIGS. 12 and 13.

[0489]FIG. 71A is an enlarged top view of the indicated portion of FIG.71 showing in greater detail gnat's wing 222, inspection channel 224,and information storage tracks 226 of the optical inspection disc 220according to this embodiment of the present invention. FIG. 71A alsoshows a focused spot 227 of the incident beam directed toward the gnatswing 222.

[0490]FIG. 72 is a cross-sectional side view taken perpendicular to aradius of optical inspection disc 220 of FIG. 71 including gnat's wing222 as the investigational feature located within inspection channel224. Gnat's wing 222 is interrogated according to the present inventionby read beam 225 of an optical disc drive assembly.

[0491]FIG. 73A is a graphical representation of a lateral section of thegnat's wing 222 of FIG. 71 as positioned in inspection channel 224relative to tracks 226 of optical inspection disc 220 according to thepresent invention.

[0492]FIG. 73B is a single signature trace derived from the section ofthe gnat's wing of FIG. 73A utilizing an AC coupled and buffered HFsignal from the optical drive according to the present invention. TheHF-AC coupled signal from HF Matrix Amp 18A (FIG. 21) of optical headassembly 174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS.22 and 23). The signal is amplified and conditioned (FIG. 24B) thendirected to output connector J3 of output section 157 (FIG. 22). Frombuffer amplifier card 152, the signal is sent to ADC 150 and isprocessed by PC 158 and imaged by monitor 146 (FIGS. 9A and 12). Asdescribed above, modified PC 142 may substitute one or more of theprocessing devices described herein. FIG. 73B reveals that a scan overan investigational feature such as gnat's wing 222 results in aperturbation of the HF signal that can be detected.

[0493]FIG. 74A is a similar graphical representation of a lateralsection of gnat's wing 222 of FIG. 71 as positioned in inspectionchannel 224 relative to tracks 226 of optical inspection disc 220according to the present invention.

[0494]FIG. 74B is a series of four consecutive signature traces derivedfrom the section of the gnat's wing of FIG. 74A utilizing an AC coupledand buffered HF signal from the optical drive according to the presentinvention. The HF-AC coupled signal from HF Matrix Amp 18A (FIG. 21) ofoptical head assembly 174 (FIG. 19) is directed to buffer amplifier card152 (FIGS. 22 and 23). The signal is amplified and conditioned (FIG.24B) then directed to output connector J3 of output section 157 (FIG.22). From buffer amplifier card 152, the signal is sent to ADC 150 andis processed by PC 158 and imaged by monitor 146 (see FIGS. 9A and 12).As described above, modified PC 142 may substitute one or more of theprocessing devices described herein. FIG. 74B reveals that consecutivetraces, scanned over an investigational feature such as gnat's wing 222,result in distinct perturbations of the HF signal that can be detected.

[0495]FIG. 75A is a similar graphical representation of a lateralsection of gnat's wing 222 of FIG. 71 as positioned in inspectionchannel 224 relative to tracks 226 of optical inspection disc 220according to the present invention.

[0496]FIG. 75B is a series of consecutive signature traces at moderatedensity derived from the section of the gnat's wing of FIG. 75Autilizing an AC coupled and buffered HF signal from the optical driveaccording to the present invention. The HF-AC coupled signal from HFMatrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (FIGS. 9A and 12). As described above, modified PC 142 maysubstitute one or more of the processing devices described herein. FIG.75B reveals that consecutive traces at moderate density, scanned over aninvestigational feature such as gnat's wing 222, result in distinctperturbations of the HF-AC signal that can be detected.

[0497]FIG. 76A is a similar graphical representation of a lateralsection of gnat's wing 222 of FIG. 71 as positioned in inspectionchannel 224 relative to tracks 226 of optical inspection disc 220according to the present invention.

[0498]FIG. 76B is a series of consecutive signature traces at higherdensity derived from the section of the gnat's wing of FIG. 76Autilizing an AC coupled and buffered HF signal from the optical driveaccording to the present invention. The HF-AC coupled signal from HFMatrix Amp 18A (FIG. 21) of optical head assembly 174 (FIG. 19) isdirected to buffer amplifier card 152 (FIGS. 22 and 23). The signal isamplified and conditioned (FIG. 24B) then directed to output connectorJ3 of output section 157 (FIG. 22). From buffer amplifier card 152, thesignal is sent to ADC 150 and is processed by PC 158 and imaged bymonitor 146 (see FIGS. 9A and 12). As described above, modified PC 142may substitute one or more of the processing devices described herein.FIG. 76B reveals that consecutive traces at higher density, scanned overan investigational feature such as gnat's wing 222, result in distinctperturbations of the HF signal that can be detected and imaged.

[0499]FIGS. 77A, 77B, and 77C are pictorial representations of thegnat's wing of FIG. 71 as rendered by imaging methods according to thepresent invention respectively utilizing either an AC coupled andbuffered HF signal, a DC coupled and buffered “A” signal, or a DCcoupled and buffered HF signal from an optical drive assembly. The HF-ACcoupled signal from HF Matrix Amp 18A (FIG. 21) of optical head assembly174 (FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and23). The signal is amplified and conditioned (FIG. 24B) then directed tooutput connector J3 of output section 157 (FIG. 22).

[0500] The HF-A coupled signal (FIG. 21) from optical head assembly 174(FIG. 19) is directed to buffer amplifier card 152 (FIGS. 22 and 23).The signal is amplified and conditioned (FIGS. 24B and 24C) thendirected to output connector J7 of output section 157 (FIG. 22).

[0501] The HF-DC coupled signal from HF Matrix Amp 18A (FIG. 21) ofoptical head assembly 174 (FIG. 19) is directed to buffer amplifier card152 (FIGS. 22 and 23). The signal is amplified and conditioned (FIG.24A) then directed to output connector J5 of output section 157 (FIG.22). From buffer amplifier card 152, the signals are sent to ADC 150 andare processed by PC 158 and imaged by monitor 146 (FIGS. 9A and 12). Asdescribed above, modified PC 142 may substitute one or more of theprocessing devices described herein. FIGS. 77A, 77B, and 77C reveal thatscans utilizing different signals produced by the optical head assemblyof the disc drive render pictorial representations of theinvestigational feature that are detectable.

[0502]FIG. 78 is a graphical representation illustrating therelationship between FIGS. 78A and 78B.

[0503]FIGS. 78A and 78B are electrical schematics of a second embodimentof the amplifier stages that may be implemented according to the presentinvention in the buffer cards shown in FIGS. 22 and 23.

[0504]FIG. 78A is a partial electrical schematic of the bufferamplifier. The analog HF-A signal from the optical head assembly 174(FIG. 19) is taken from pins 19 and 14 of connector 155 (FIGS. 22 and23). The input signal travels across an input load resistor and avoltage, stabilization capacitor to equalize background noise betweenthe positive and negative leads. The positive signal is then fed into anop amp, which is buffered with a feedback loop. The amplified signal isdirected across an output load resistor.

[0505] The analog HF-B signal from the optical head assembly 174 istaken from pins 17 and 16 of connector 155 (FIGS. 22 and 23). As above,the signal is amplified and buffered.

[0506] The analog HF-C signal from the optical head assembly 174 istaken from pins 15 and 18 of connector 155 (FIGS. 22 and 23). As above,the signal is amplified and buffered.

[0507] The analog HF-D signal from the optical head assembly 174 istaken from pins 13 and 20 of connector 155 (FIGS. 22 and 23). As above,the signal is amplified and buffered.

[0508]FIG. 78B is a partial electrical schematic of the bufferamplifier. Amplified signals HF-A, HF-B, HF-C, and HF-D pass throughindependent load resistors and are combined. The combined signal is fedinto the negative input of an op amp, which is fed a variable positivesignal. The amplified signal is buffered by a feedback loop, anddirected across a variable load resistor before being fed into thenegative input of another op amp. The amplified signal is buffered by afeedback loop and conditioned by an array of capacitors with a coil. Theconditioned signal is then fed into the positive input of an op amp,which is buffered by a feedback loop. The amplified signal is thendirected across an output load resistor and stabilization capacitor andis output at connector J6 of output section 157 (FIG. 22).

[0509] Optical Bio-Discs for Biological and Chemical Assays

[0510] The following discussion is directed to the biological andchemical applications for which the invention is useful. In sequencingapplications, a sequence of nucleotide bases within the DNA sample canbe determined by detecting which probes have the DNA sample boundthereto. In diagnostic applications, a genomic sample from an individualis screened against a predetermined set of probes to determine if theindividual has a disease or a genetic disposition to a disease.

[0511] This invention combines microfluidic technology with genomics andproteomics on an optical bio-disc to detect investigational features ina test sample. Referring to FIGS. 79A, 79B, 79C, and 79D, an aqueoustest sample 252 is placed on or within an optical bio-disc 250 and isdriven through micro-channels 254 across a specially prepared surface256 to effectuate the desired tests. Capillary action, pressure appliedwith an external applicator, and/or centrifugal force (i.e., the forceon a body in curvilinear motion directed away from the center orcurvature or axis of rotation) act upon the test sample to achievecontact with capture probes 258. Nucleic acid probe technology hasapplication in detection of genetic mutations and related mechanisms,cancer screening, determining drug toxicity levels, detection of geneticdisorders, detection of infectious disease, and genetic fingerprinting.

[0512] Additionally, the invention is adapted for use in a mixed phasesystem to perform hybridization assays. Referring to FIGS. 80A, 80B,80C, and 80D, a mixed phase assay involves performing hybridizations ona solid phase such as a thin nylon or nitrocellulose membrane 262. Forexample, the assays usually involve spin-coating a thin layer ofnitrocellulose 262 onto the substrate 264 of a bio-disc 260, using apipette 266 or similar device to load the membrane with a sample 268,denaturing the DNA or creating single stranded molecules 270, fixing theDNA or RNA to the membrane, and saturating the remaining membraneattachment sites with heterologous nucleic acids and/or proteins 272 toprevent the analytes and reporters from adhering to the membrane in anon-specific manner. All of these steps must be carried out beforeperforming the actual hybridization. Subsequent steps are then performedto achieve hybridization and locate reporter beads in the capture areasor target zones. The incident beam is then utilized to detect thereporters as discussed in reference to FIG. 79.

[0513] Optical bio-discs are useful for experimental analysis and assaysin the areas of genetics and proteomics in applications as diverse aspharmaco-genomics, gene expression, compound screening, toxicology,forensic investigation, Single Nucleotide Polymorphism (SNPs) analysis,Short Tandem Repeats (STRs), and clinical/molecular diagnostics.

[0514] Reporters

[0515] Many chemical, biochemical, and biological assays rely uponinducing a change in the optical properties of the particular samplebeing tested. Such a change may occur upon detection of theinvestigational feature itself (e.g., blood cells), or upon detection ofa reporter. In the case where investigational features are too small tobe detected by the read beam of the optical disc drive, reporters havinga selective affinity (i.e., a tendency to react or combine with atoms orcompounds of different chemical constitution for the investigationalfeatures within the test sample) for the investigational feature tofacilitate detection. The reporter will react, combine, or otherwisebind to the investigational feature, thereby causing a detectable color,chemiluminescent, luminescent, or other identifiable label into theinvestigational feature.

[0516] Luminescence is formally divided into two categories,fluorescence and phosphorescence, depending on the nature of the excitedstate. A luminescent molecule has the ability to absorb photons ofenergy at one wavelength and subsequently emit the energy at anotherwavelength. Luminescence is caused by incident radiation impinging uponor exciting an electron of a molecule. The electron absorbs the incidentradiation and is raised from a lower quantum energy level to a higherone. The excess energy is released as photons of light as the electronreturns to the lower, ground-state energy level. Since each reporter hasits own luminescent character, more than one labeled molecule, eachtagged with a different reporter, can be used at the same time to detecttwo or more investigational features within the same test sample.

[0517] In addition to luminescence, techniques such as color stainingusing an enzyme-linked immunosorbent assay (ELISA) and gold labeling canbe used to alter the optical properties of biological antigen material.For example, in order to test for the presence of an antibody in a bloodsample, possibly indicating a viral infection, an ELISA can be carriedout which produces a visible colored deposit if the antibody is present.Referring to FIGS. 81A, 81B, 81C, 81D, 81E, and 81F, an ELISA makes useof a surface 280 that is coated with an antigen 282 specific to theantibody 284 to be tested for. Upon exposure of the surface to the bloodsample 286, antibodies in the sample bind to the antigens. Subsequentstaining of the surface with specific enzyme-conjugated antibodies 288and reaction of the enzyme with a substrate produces a precipitate 290that correlates with the level of antigen binding and hence allows thepresence of antibodies in the sample to be identified by the opticaldisc drive. This precipitate is then detected by the incident beam.Further details relating to use of precipitates as a reporting mechanismare disclosed in U.S. Provisional Application No. 60/292,110 entitled“Surface Assembly for Immobilizing DNA Capture Probes Using Pellets asReporters in Genetic Assays Including Optical Bio-Discs and MethodsRelating Thereto” filed May 18,2001 and U.S. Provisional Application No.60/313,917 entitled “Surface Assembly for Immobilizing DNA CaptureProbes in Genetic Assays Using Enzymatic Reactions to Generate Signal inOptical Bio-Discs and Methods Relating Thereto” filed Aug. 21, 2001,both of which are herein incorporated by reference.

[0518] Referring to FIG. 82, bead-based assays involve use of sphericalmicro-particles, or beads 300 to alter the optical properties ofbiological antigen material 302. The beads 300 are coated with achemical layer 304 having a specific affinity for the investigationalfeature in a test sample. Referring to FIGS. 83A, 83B, 83C, and 83D,when a test sample is loaded into or onto an optical disc 310 containingreporter beads 300 (FIG. 82), the investigational feature 312, ifpresent, binds to the reporter beads 300. Investigational feature 312further binds to specific capture agents 314 on the surface 316 of theoptical disc 310. In this way, if the investigational feature is presentin the biological solution, it becomes a binding agent to bind beadreporters 300 to capture agents 314 on the surface 316 of the bio-disc310. When the bio-disc is spun in the optical disc drive, the resultingcentrifugal force sends unbound bead reporters 318 to an outer peripheryof the disc, while bound bead reporters remain distributed over the areaof the disc coated with the capture agent. The bound beads can bedetected and quantified using an optical disc reader. Related dual beadassays are further disclosed in commonly assigned, co-pending U.S.patent application Ser. No. 09/997,741 entitled “Dual Bead AssaysIncluding Optical Biodiscs and Methods Relating Thereto” filed Nov. 27,2001, which is incorporated herein by reference.

[0519] Reporters useful in the invention include, but are not limitedto, synthetic or biologically produced nucleic acid sequences, syntheticor biologically produced ligand-binding amino acids sequences, productsof enzymatic reactions, and plastic micro-spheres or beads made of, forexample, latex, polystyrene or colloidal gold particles with coatings ofbio-molecules that have an affinity for a given material such as abiotin molecule in a strand of DNA. Appropriate coatings include thosemade from streptavidin or neutravidin, for example. These beads areselected in size so that the read or interrogation beam of the opticaldisc drive can “see” or detect a change of surface reflectivity causedby the particles.

[0520] In some embodiments associated with the present invention,reporter beads are bound to the disc surface through DNA hybridization.Referring to FIGS. 84 and 85, a capture probe 332 is attached to thedisc surface 330, while a signal probe 334 is attached to reporter beads300 (FIG. 82). In the case of a hybridization assay, both of the probesare complementary to the target sequence 336. In the presence of targetsequence 336, both capture and signal probes hybridize with the target.In this manner, beads 300 are attached to disc surface 330. In asubsequent centrifugation (or wash) step, all unbound beads are removed.Alternatively, the target itself is directly bound or linked to thebeads without the presence of an extra signaling probe.

[0521] Referring to FIG. 86, in the case of an immunoassay, the discsurface 340 is coated with a receptor 342 (e.g., antibody), whichspecifically binds to the analyte of interest 344 (e.g., investigationalfeature). The capture zones 346 for each specific analyte to be assayedcould be separated in the analysis field of the disc. If an analyte 344(antigen or antibody) is captured by the receptor 342 (antibody orantigen, respectively), present on the capture zone 346, then a signalgeneration combination specific for the analyte can be used to quantifythe presence of the analyte.

[0522] Alternatively, an investigational feature, if of adequate sizefor detection by the incident beam of an optical disc drive, may notrequire a reporter. Certain chemical reactions and the products andby-products resulting therefrom (i.e., precipitates), induce asufficient change in the optical properties of the biological samplebeing tested. Such a change may also occur upon detection of theinvestigation feature itself, such as is the case when the invention isused to create an image of a microscopic structure. The optical discdrive detects changes in the optical properties of the surface of thebio-disc and creates images based thereon.

[0523] In a particular embodiment of the invention, an optical discsystem (e.g., FIGS. 9A and 12) includes a signal processing system(e.g., 142, or 158 and 156, or 158 and 32 with or without 154, or 158and 150 with or without 152 of FIG. 9A) and a photo detector circuit(e.g., 18 of FIG. 1) of an optical disc drive configured to generate atleast one information-carrying signal (e.g., the HF, TE, or FE signals)from an optical disc assembly (e.g., disc 130 of FIG. 12). The signalprocessing system is coupled to the photo detector 18 to obtain from theat least one information-carrying signal both operational information(e.g., tracking, focusing and speed signals of FIG. 8) used to operatethe optical disc system and indicia data (e.g., traces in FIG. 61B)indicative of a presence of an investigational feature (e.g.,investigational feature 68 of FIG. 43) associated with the optical discassembly.

[0524] In a variant of the invention, the signal processing system ofthe optical disc system includes a PC and an analog-to-digital converterto provide a digitized signal to the PC. The analog-to-digital converteris coupled between the at least one information carrying signal and thePC. The PC includes a program module to detect and characterize peaks(e.g., see traces in FIG. 61B) in the digitized signal. Preferably, thePC further includes another program module to detect and count doublepeaks (e.g., see traces D and E in FIG. 61B) in the digitized signal.

[0525] In another variant of the invention, the signal processing systemof the optical disc system includes a PC, an analog-to-digital converterto provide a digitized signal to the PC, and an analyzer 154(implementation III of FIG. 9A) coupled between the analog-to-digitalconverter (e.g., the converter in 32 of FIG. 8) and the PC. Theanalog-to-digital converter is coupled between the at least oneinformation carrying signal and the PC. The analyzer includes logic todetect and characterize peaks in the digitized signal. Preferably, theanalyzer further includes logic to detect and count double peaks in thedigitized signal.

[0526] In still another variant of the invention, the signal processingsystem of the optical disc system includes a PC and an analog-to-digitalconverter to provide a digitized signal to the PC (implementation IV ofFIG. 9A). The analog-to-digital converter is coupled between the atleast one information carrying signal and the PC. The signal processingsystem further includes an audio processing module (e.g., 156 of FIG.9A) coupled between the at least one information-carrying signal and theanalog-to-digital converter. Preferably, the optical disc assembly ispre-recorded with a predetermined sound, and the PC includes a programmodule to detect the indicia data in a deviation of the at least oneinformation carrying signal from the predetermined sound when theinvestigational feature is present. In an alternative variant, thepredetermined sound is encoded silence.

[0527] In still yet another variant of the invention, the signalprocessing system of the optical disc system includes a PC and ananalog-to-digital converter to provide a digitized signal to the PC(implementation II of FIG. 9A). The analog-to-digital converter iscoupled between the at least one information carrying signal and the PC.The signal processing system further includes an external bufferamplifier (e.g., 152 of FIG. 9A) coupled between the at least oneinformation-carrying signal and the analog-to-digital converter.

[0528] In a further variant of the invention, the signal processingsystem of the optical disc system includes a PC and an analog-to-digitalconverter to provide a digitized signal to the PC. The analog-to-digitalconverter is coupled between the at least one information carryingsignal and the PC. The signal processing system further includes atrigger detection circuit (e.g., 164 of FIG. 12) coupled to theanalog-to-digital converter. The trigger detection circuit is operativeto detect a particular time in relation to a time when the indicia datais present in the at least one information-carrying signal.

[0529] In an alternative embodiment, the signal processing systemincludes a programmable digital signal processor selectivelyconfigurable to either (1) extract the operational information from theat least one information-carrying signal while in a first configurationor (2) operate as an analog-to-digital converter to provide the indiciadata while in a second configuration. For example, see FIG. 25 andimplementation III of FIG. 9A.

[0530] In another alternative embodiment, the signal processing systemof the optical disc system includes a PC (e.g., 158 of FIG. 9A), aprogrammable digital signal processor (e.g., 32 of FIG. 9A) coupled tothe at least one information-carrying signal, and an analyzer (e.g., 154of FIG. 9A) coupled between the programmable digital signal processorand the PC. The analyzer provides the indicia data as depicted inimplementation III of FIG. 9A.

[0531] In yet another alternative embodiment, the signal processingsystem of the optical disc system includes a trigger detection circuit(e.g., 164 of FIG. 12) that detects a time period during which theinvestigational feature associated with the optical disc assembly isscanned by the photo detector circuit.

[0532] In a further alternative embodiment, the signal processing systemof the optical disc system includes a trigger detection circuit (e.g.,164 of FIG. 12) that detects a particular time in relation to a timewhen the indicia data is present in the at least oneinformation-carrying signal. The time when the indicia data is presentin the at least one information-carrying signal occurs periodically. Theparticular time is either (1) a predetermined time in advance of, (2) atime at, or (3) a predetermined time after each time the indicia dataeither begins to be present or ends in the at least oneinformation-carrying signal.

[0533] In still yet another alternative embodiment, the signalprocessing system of the optical disc system includes a PC (e.g., 158 ofFIG. 9A), and an audio processing module (e.g., 156 of FIG. 9A) coupledbetween the PC and the at least one information-carrying signal.Preferably, the sound processing module is either an external moduleindependent of the optical disc drive, a drive module that is a part ofthe optical disc drive, or a modified drive module that is a part of theoptical disc drive. In a variant of this embodiment, the PC includes aprocessor coupled to the sound module, and a software module stored in amemory to control the processor to extract the indicia data from sounddata (e.g., see implementation IV of FIG. 9A).

[0534] In yet a further alternative embodiment, the photo detectorcircuit of the optical disc system includes circuitry to generate ananalog signal as the at least one information-carrying signal. Theanalog signal includes either a high frequency signal from a photodetector, a tracking error signal, a focus error signal, an automaticgain control setting, a push-pull tracking signal, a CD tracking signal,a CD-R tracking signal, a focus signal, a differential phase detectorsignal, a laser power monitor signal or a sound signal.

[0535] In another embodiment, the optical disc system further includesthe optical disc assembly (e.g., 130 of FIG. 12). The optical discassembly has the associated investigational feature (e.g., 136 of FIG.12) disposed on the assembly in a first disc sector and has theoperational information (e.g., 133 of FIG. 12) used to operate theoptical disc drive encoded on the assembly in a remaining disc sector.

[0536] In a variant, the optical disc assembly includes a trigger mark(e.g., 166 of FIG. 12) that is disposed on the optical disc assembly ina predetermined position relative to the first disc sector. The signalprocessing system further includes a trigger detection circuit (e.g.,164 of FIG. 12) that detects the trigger mark. Preferably, the triggerdetection circuit detects the trigger mark periodically and detects thetrigger mark either (1) a predetermined time in advance of, (2) a timeat, or (3) a predetermined time after a time when the associatedinvestigational feature is read by the photo detector circuit based onthe predetermined position of the trigger mark relative to the firstdisc sector.

[0537] In a variant, the associated investigational feature of theoptical disc assembly includes either plastic micro-spheres with abio-molecule coating, colloidal gold beads with a bio-molecule coating,silica beads, glass beads, magnetic beads, or fluorescent beads.

[0538] In another embodiment of the invention, there is provided amethod that includes the steps of depositing a test sample, spinning theoptical disc, directing an incident beam, detecting a return beam,processing the detected return beam, and processing the detected returnbeam. The step of depositing a test sample includes depositing thesample at a predetermined location on an optical disc assembly. The stepof spinning the optical disc includes spinning the assembly in anoptical disc drive. The step of directing an incident beam includesdirecting the beam onto the optical disc assembly. The step of detectinga return beam includes detecting the return beam formed as a result ofthe incident beam interacting with the test sample. The step ofprocessing the detected return beam processes the detected return beamto acquire information about an investigational feature associated withthe test sample.

[0539] In a variant of this embodiment, the step of detecting a returnbeam forms a plurality of analog signals. The step of processing thedetected return beam includes summing a first subset of the plurality ofanalog signals to produce a sum signal, combining either the firstsubset or a second subset of the plurality of analog signals to producea tracking error signal, obtaining information used to operate anoptical disc drive from the tracking error signal, and converting thesum signal to a digitized signal.

[0540] In another embodiment of the invention, the invention is a methodthat includes steps of acquiring a plurality of analog signals, summinga first subset, combining a second subset, obtaining information, andconverting the sum signal to a digitized signal. The step of acquiring aplurality of analog signals acquires analog signals from an optical discassembly using a plurality of photo detectors. The step of summing afirst subset sums a first subset of the plurality of analog signals toproduce a sum signal. The step of combining a second subset combines asecond subset of the plurality of analog signals to produce a trackingerror signal. The step of obtaining information obtains information usedto operate an optical disc drive from the tracking error signal.

[0541] In a variant, the steps of acquiring and summing produce the sumsignal that includes perturbations indicative of an investigationalfeature located at a location of the optical disc assembly.

[0542] In another variant, the method further includes a step ofcharacterizing the investigational feature based on the digitizedsignal.

[0543] In another variant of the method, the step of converting includesconfiguring a portion of an optical disc drive chip set to operate as ananalog-to-digital converter. Preferably, the step of configuringincludes programming a digital signal processing chip within the opticaldisc drive chip set to operate as an analog-to-digital converter.Preferably, the digital signal processing chip includes a normalizationfunction, an analog-to-digital converter function, a demodulation/decodefunction, and an output interface function. Preferably, the step ofconfiguring further includes passing the sum signal around thedemodulation/decode function by creating a path from theanalog-to-digital converter function to the output interface function.Preferably, the step of configuring further includes deactivating thedemodulation/decode function.

[0544] In another variant of the method, the step of converting includesconfiguring a digital signal processing chip that includes anormalization function, an analog-to-digital converter function, ademodulation/decode function, and an output interface function, and thestep of configuring includes creating a path from the analog-to-digitalconverter function to the output interface function so that the sumsignal is unprocessed by the demodulation/decode function. Preferably,the step of configuring includes deactivating the demodulation/decodefunction.

[0545] In yet another embodiment of the invention, a method includessteps of adapting a portion of a signal processing system, acquiring aplurality on analog signals, converting the analog signals, andcharacterizing investigational features based on a digitized signal. Thestep of adapting a portion of a signal processing system includesadapting the portion to operate as an analog-to-digital converter. Thestep of acquiring a plurality on analog signals acquires the analogsignals from a photo detector circuit of an optical disc drive. Theplurality of analog signals includes information that is indicative ofinvestigational features on an optical disc assembly. The step ofconverting the analog signals converts the analog signals into adigitized signal with the signal processing system. Preferably, the stepof adapting includes programming a digital signal processing chip withinthe signal processing system to operate as the analog-to-digitalconverter.

[0546] In another alternative embodiment of the invention, a methodincludes steps of receiving and converting. The step of receivingincludes receiving each of at least one analog signal at a correspondinginput of signal processing circuitry. The at least one analog signal hasbeen provided by at least one corresponding photo detector element thatdetects light returned from a surface of an optical disc assembly. Thestep of converting includes converting each of the at least one analogsignal into a corresponding digitized signal. Each digitized signal issubstantially proportional to an intensity of the returned lightdetected by a corresponding one of the at least one photo detectorelement.

[0547] In a variant of this embodiment, the step of converting includesoperating the signal processing circuitry to bypass any demodulation ofa first digitized signal. Preferably, the step of converting furtherincludes operating the signal processing circuitry to bypass anydecoding of the first digitized signal, and operating the signalprocessing circuitry to bypass any checking for errors in the firstdigitized signal.

[0548] In another variant of this embodiment, the step of convertingincludes operating the signal processing circuitry to bypass anydecoding of a first digitized signal.

[0549] In yet another variant of this embodiment, the step of convertingincludes operating the signal processing circuitry to bypass anychecking for errors in a first digitized signal.

[0550] In still another variant of this embodiment, the method furtherincludes a step of combining at least two of the at least one analogsignal. Preferably, the step of combining is a step selected from agroup consisting of adding, subtracting, dividing, multiplying, and acombination thereof. Preferably, the step of combining is performedbefore the step of converting. Alternatively, the step of combining maybe performed after the step of converting.

[0551] In a further variant, the method further includes a step ofsupplying a first digitized signal of the at least one digitized signalat an output interface of the signal processing circuitry after the stepof converting without substantially modifying the first digitized signalbetween the steps of converting and supplying. Preferably, the signalprocessing circuitry includes a digital signal processor. Preferably,the signal processing circuitry consists of a digital signal processor.

[0552] The materials for use in the method of the invention are ideallysuited for the preparation of a kit. Such a kit may include a carriermember being compartmentalized to receive in close confinement anoptical bio-disc and one or more containers such as vials, tubes, andthe like, each of the containers including a separate element to be usedin the method. For example, one of the containers may include a reporterand/or protein-specific binding reagent, such as an antibody. Anothercontainer may include isolated nucleic acids, antibodies, proteins,and/or reagents described herein, known in the art or developed in thefuture. The constituents may be present in liquid or lyophilized form,as desired. The antibodies used in the assay kits of the presentinvention may be monoclonal or polyclonal antibodies. For convenience,one may also provide the reporter affixed to the substrate of thebio-disc. Additionally, the reporters may further be combined with anindicator, (e.g., a radioactive label or an enzyme) useful in assaysdeveloped in the future. A typical kit also includes a set ofinstructions for any or all of the methods described herein.

[0553] In a variant of this embodiment, the carrier may be furthercompartmentalized to include a setup optical disc containing softwarefor configuring a computer for use with the bio-disc. Optionally, thekit may be packaged with a modified optical disc drive. For example, thekit may be sold for educational purposes as an alternative to the commonmicroscope.

[0554] While this invention has been described in detail with referenceto a certain preferred embodiments, it should be appreciated that thepresent invention is not limited to those precise embodiments. Rather,in view of the present disclosure, which describes the current best modefor practicing the invention, many modifications and variations wouldpresent themselves to those of skill in the art without departing fromthe scope and spirit of this invention. The scope of the invention is,therefore, indicated by the following claims rather than by theforegoing description. All changes, modifications, and variations comingwithin the meaning and range of equivalency of the claims are to beconsidered within their scope.

[0555] Having thus described the invention with the details andparticularity required by the patent laws, what is claimed and desiredprotected by Letters Patent is set forth in the appended claims.

What I claim is:
 1. An optical disc system, comprising: an objectiveassembly for sending an incident beam toward an optical disc with anair-incident surface carrying at least one investigational feature; aphoto detector circuit of an optical disc drive configured to generateat least one information-carrying signal from an optical disc assembly;a signal processing system coupled to the photo detector circuit toobtain from said at least one information-carrying signal bothoperational information used to operate the optical disc system andindicia data indicative of a presence of said investigational feature;and an adjustment lens coupled at the exit position on an said objectiveassembly whereby said incident beam is refracted to allow said opticaldisc system to read said optical disc.
 2. The optical disc system ofclaim 1 wherein said signal processing system further comprises adetection mechanism that uses signal generated by the automatic gaincontrol system within said signal processing system.
 3. The optical discsystem of claim 1 wherein said signal processing system furthercomprises a detection mechanism that uses signal generated by thefocusing servo within said optical disc system to detect the presence ofsaid investigational feature on said optical disc.
 4. The optical discsystem of claim 1 wherein said signal processing system furthercomprises a detection mechanism that uses signal generated by thetracking servo within said optical disc system to detect the presence ofsaid investigational feature on said optical disc.
 5. The optical discsystem of claim 1 wherein said signal processing system furthercomprises a detection mechanism that uses signal generated by the powercontrol mechanism within said optical disc system to detect the presenceof said investigational feature on said optical disc.
 6. The opticaldisc system of claim 1 wherein said signal processing system furthercomprises a detection mechanism that uses signal generated by thesynchronization mechanism within said optical disc system to detect thepresence of said investigational feature on said optical disc.
 7. Theoptical disc system of claim 1 wherein said signal processing systemfurther comprises a detection mechanism that uses signal generated bythe encoding and decoding mechanism within said signal processing systemto detect the presence of investigational feature on said optical disc.8. The optical disc system of claim 1 wherein said signal processingsystem further comprises: a channel bit generator wherein known gooddata bits are generated and added to data bits received from saidinformational-carrying signal to produce a sum of bits; and a blockdecoder whereby said sum of bits is sent to said block decoder whereinblock error information can be obtained.
 9. The optical disc system ofclaim 1 further comprises a prism whereby the birefringent properties ofan area of said optical disc is measured.
 10. The optical disc system ofclaim 1 wherein said signal processing system further includes a lookuptable optimized for the detection of said investigational feature. 11.The optical disc system of claim 1 further comprises a solid immersionlens.
 12. The optical disc system of claim 1 wherein the signalprocessing system includes programming logic to read error codes in thedecoder of said optical disc system and detect the presence of saidinvestigational feature.
 13. The optical disc system of claim 1 whereinsaid optical disc is a reverse wobble image optical disc.
 14. Theoptical disc system of claim 1 wherein said optical disc contains aembedded data mask for enhancing an error signal caused by saidinvestigational feature.
 15. The optical disc system of claim 1 whereinsaid signal processing system further includes a trigger detectioncircuit that detects a registration mark on said optical disc, whereinsaid registration mark uses autocorrelation codes to trigger thebeginning and end of a detection period.
 16. A method of modifying anoptical disc system for the purpose of detecting investigational featureon an optical disc comprising the step of: modifying the circuitry ofsaid optical disc system whereby operational features are used to detectsaid investigational feature.
 17. The method of claim 16 furthercomprises the step of implementing wobble groove playback and randomaccess on a wobble groove.
 18. The method of claim 16 further comprisesthe step of adding a polling monitor to the laser monitor value wherebythe reading detected by the laser power monitor detector in the opticalpickup unit in said optical disc system is accessed.
 19. The method ofclaim 16 further comprises the step of adding a poll to the automaticgain control value in said optical disc system.
 20. The method of claim16 further comprises the step of adding a poll to the tracking automaticgain control value.
 21. The method of claim 16 further comprises thestep of adding a monitor to the C1 decoder.
 22. The method of claim 16further comprises the step of adding a monitor to the C2 decoder. 23.The method of claim 16 further comprises the step of adding overridingcontrol logic whereby said optical disc system initialize and trackoperational features on said disc independent of encoded logic.
 24. Themethod of claim 16 further comprises the step of adding control logicwhereby user can initialize said optical disc system with a specificspeed and laser read power.
 25. The method of claim 16 further comprisesthe step of streaming the main and sub-channel data of said optical discincluding lead-in and lead-out.
 26. The method of claim 16 furthercomprises the step of adding an electrical line that pushes raw-EFMvalue to a port wherein user can see the 14-bit data before it istranslated to 8-bit values.
 27. The method of claim 16 further comprisesthe step of adding electrical lines to push one of a group of data, saidgroup comprising buffered signal, DC coupled signals, TE, FE and HF, toan external port for additional processing.
 28. The method of claim 16further comprises the step of adding mechanism to decode and poll valuescollected from the power calibration area and program memory area ofsaid optical disc at initialization.
 29. The method of claim 16 furthercomprises the step of pausing playback of said optical disc and open thetracking servo to monitor the open loop tracking signal.
 30. The methodof claim 16 further comprises the step of setting Ghost initializationlogic whereby said optical disc system can be configured to skip readingthe table of contents from said optical disc.
 31. The method of claim 16further comprises the step of interactively turning off trackingfunction of said optical disc system.
 32. The method of claim 16 furthercomprises the step of using the focusing mechanism of said optical discsystem to heat up regions of said optical disc.
 33. The method of claim16 further comprises the step of loading new logic onto said opticaldisc system by using EEPROM on said optical disc system.
 34. A method ofmodifying a DVD optical disc system for the purpose of detectinginvestigational feature on a DVD optical disc comprising the step of:modifying the circuitry of said optical disc system whereby operationalfeatures are used to detect said investigational feature.
 35. The methodof claim 34 further comprises the step of switching the layers on saidDVD optical disc.
 36. The method of claim 34 further comprises the stepof using in laser in said DVD optical disc system to read a CD or CD-RWoptical disc.
 37. The method of claim 34 further comprises the step ofusing the laser in said DVD optical disc system to track a wobble grooveat any frequency.
 38. The method of claim 34 further comprises the stepof adding a monitor to the value of a buffered differential phasedetection signal generated by the tracking mechanism of said DVD opticaldisc system.
 39. An optical analysis disc for use in imaging abiological or medical investigational feature, comprising: a substrate;an operational layer associated with said substrate layer, saidoperational layer having operational information encoded therein,wherein said operational layer comprises of wobble groove tracksspiraling from the center of said optical analysis disc; and aninvestigational feature positioned relative to said operational layerand said operational layer having optical or magnetic characteristicsselected to provide a predetermined contrast therebetween to therebyprovide a return signal indicative of distinctions between informationassociated with said operation layer and characteristics of saidinvestigational feature and whereby said wobble groove is configured toisolate the tracking signal from the HF or Quad sum signal.
 40. Amulti-layer optical analysis disc for use in imaging a biological ormedical investigational feature, comprising: an operational layer havingoperational information encoded therein, wherein said operational layercomprises of wobble groove tracks spiraling from the center of saidoptical analysis disc; and a larger second layer attached to saidoperational layer having an investigational feature and said operationallayer having optical or magnetic characteristics selected to provide apredetermined contrast therebetween to thereby provide a return signalindicative of distinctions between information associated with saidoperation layer and characteristics of said investigational feature.